<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019e65e1-5158-7519-aa58-4c0341498059,g:ddebbfab-f5f9-4f81-804f-a889ba20ff0b-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.pliantrx.com/role/Cover" xlink:type="simple" xlink:href="plrx-20260630.xsd#Cover"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/Cover" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_DocumentInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentInformationTable_019e65e1-522a-70e6-86f3-bdb6a785b7ba" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_DocumentInformationTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_DocumentInformationTable_019e65e1-522a-70e6-86f3-bdb6a785b7ba" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_019e65e1-522a-7b89-a29d-81026e62abff" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_dei_DocumentInformationTable_019e65e1-522a-70e6-86f3-bdb6a785b7ba" xlink:to="loc_us-gaap_StatementClassOfStockAxis_019e65e1-522a-7b89-a29d-81026e62abff" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-7b89-a29d-81026e62abff_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019e65e1-522a-7b89-a29d-81026e62abff" xlink:to="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-7b89-a29d-81026e62abff_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-7106-a424-46d48e518492" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019e65e1-522a-7b89-a29d-81026e62abff" xlink:to="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-7106-a424-46d48e518492" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_CommonStockParValue0.0001PerShareMember_019e65e1-522a-7002-9c7d-bcc0ee05ee5a" xlink:href="plrx-20260630.xsd#plrx_CommonStockParValue0.0001PerShareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-7106-a424-46d48e518492" xlink:to="loc_plrx_CommonStockParValue0.0001PerShareMember_019e65e1-522a-7002-9c7d-bcc0ee05ee5a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_SeriesAJuniorParticipatingPreferredPurchaseRightsMember_019e65e1-522a-7a39-8ba9-2114523a649c" xlink:href="plrx-20260630.xsd#plrx_SeriesAJuniorParticipatingPreferredPurchaseRightsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-7106-a424-46d48e518492" xlink:to="loc_plrx_SeriesAJuniorParticipatingPreferredPurchaseRightsMember_019e65e1-522a-7a39-8ba9-2114523a649c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentType_019e65e1-522a-7dc2-a05d-8a64568c4d25" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_DocumentType"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_DocumentType_019e65e1-522a-7dc2-a05d-8a64568c4d25" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentQuarterlyReport_019e65e1-522a-7804-9205-f359ddbc7b07" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_DocumentQuarterlyReport"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_DocumentQuarterlyReport_019e65e1-522a-7804-9205-f359ddbc7b07" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentPeriodEndDate_019e65e1-522a-78d8-abf9-17df0206e35a" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_DocumentPeriodEndDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_DocumentPeriodEndDate_019e65e1-522a-78d8-abf9-17df0206e35a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentTransitionReport_019e65e1-522a-7d15-9d1c-d9c84e3063b4" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_DocumentTransitionReport"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_DocumentTransitionReport_019e65e1-522a-7d15-9d1c-d9c84e3063b4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityFileNumber_019e65e1-522a-7408-a468-6680542ce54a" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityFileNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityFileNumber_019e65e1-522a-7408-a468-6680542ce54a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityRegistrantName_019e65e1-522a-7901-9891-14ee4b49edcd" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityRegistrantName"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityRegistrantName_019e65e1-522a-7901-9891-14ee4b49edcd" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityIncorporationStateCountryCode_019e65e1-522a-749f-b76c-7375a55739cd" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityIncorporationStateCountryCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityIncorporationStateCountryCode_019e65e1-522a-749f-b76c-7375a55739cd" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityTaxIdentificationNumber_019e65e1-522a-7ff3-9a5e-dff66144d3fa" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityTaxIdentificationNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityTaxIdentificationNumber_019e65e1-522a-7ff3-9a5e-dff66144d3fa" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressAddressLine1_019e65e1-522a-713e-b7d7-0e02534d847b" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityAddressAddressLine1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityAddressAddressLine1_019e65e1-522a-713e-b7d7-0e02534d847b" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressCityOrTown_019e65e1-522a-7b88-98ec-dad66cdcdfdf" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityAddressCityOrTown"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityAddressCityOrTown_019e65e1-522a-7b88-98ec-dad66cdcdfdf" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressStateOrProvince_019e65e1-522a-7ad3-8bb5-883e1f2a66b9" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityAddressStateOrProvince"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityAddressStateOrProvince_019e65e1-522a-7ad3-8bb5-883e1f2a66b9" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityAddressPostalZipCode_019e65e1-522a-7dc9-861d-aeb82eef2fc6" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityAddressPostalZipCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityAddressPostalZipCode_019e65e1-522a-7dc9-861d-aeb82eef2fc6" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_CityAreaCode_019e65e1-522a-7704-a9fc-ac5ffd2b7e07" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_CityAreaCode"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_CityAreaCode_019e65e1-522a-7704-a9fc-ac5ffd2b7e07" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LocalPhoneNumber_019e65e1-522a-74d2-af36-2eb75efd7aa3" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_LocalPhoneNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_LocalPhoneNumber_019e65e1-522a-74d2-af36-2eb75efd7aa3" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_Security12bTitle_019e65e1-522a-7043-9530-ea1764cb4d79" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_Security12bTitle"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_Security12bTitle_019e65e1-522a-7043-9530-ea1764cb4d79" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_TradingSymbol_019e65e1-522a-764a-9309-8d117c570c37" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_TradingSymbol"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_TradingSymbol_019e65e1-522a-764a-9309-8d117c570c37" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_NoTradingSymbolFlag_019e65e1-522a-71f8-a963-5859f3c40c42" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_NoTradingSymbolFlag"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_NoTradingSymbolFlag_019e65e1-522a-71f8-a963-5859f3c40c42" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_SecurityExchangeName_019e65e1-522a-7237-ba28-bcee213f8677" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_SecurityExchangeName"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_SecurityExchangeName_019e65e1-522a-7237-ba28-bcee213f8677" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCurrentReportingStatus_019e65e1-522a-7082-980a-b18c023c77c5" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityCurrentReportingStatus"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityCurrentReportingStatus_019e65e1-522a-7082-980a-b18c023c77c5" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityInteractiveDataCurrent_019e65e1-522a-7c38-8fd5-83e5138d693b" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityInteractiveDataCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityInteractiveDataCurrent_019e65e1-522a-7c38-8fd5-83e5138d693b" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityFilerCategory_019e65e1-522a-7e78-8ee1-2de010bd7bdb" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityFilerCategory"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityFilerCategory_019e65e1-522a-7e78-8ee1-2de010bd7bdb" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntitySmallBusiness_019e65e1-522a-78ee-81f0-a6308f750fe2" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntitySmallBusiness"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntitySmallBusiness_019e65e1-522a-78ee-81f0-a6308f750fe2" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityEmergingGrowthCompany_019e65e1-522a-7de8-bb30-ddf650a355e5" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityEmergingGrowthCompany"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityEmergingGrowthCompany_019e65e1-522a-7de8-bb30-ddf650a355e5" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityShellCompany_019e65e1-522a-7e42-8fc3-790d03def4f5" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityShellCompany"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityShellCompany_019e65e1-522a-7e42-8fc3-790d03def4f5" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCommonStockSharesOutstanding_019e65e1-522a-7e90-85e8-8df3e1eb5281" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityCommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityCommonStockSharesOutstanding_019e65e1-522a-7e90-85e8-8df3e1eb5281" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_AmendmentFlag_019e65e1-522a-7534-bba1-d09d017d275b" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_AmendmentFlag"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_AmendmentFlag_019e65e1-522a-7534-bba1-d09d017d275b" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentFiscalYearFocus_019e65e1-522a-7563-92fe-adbf81950a9e" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_DocumentFiscalYearFocus"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_DocumentFiscalYearFocus_019e65e1-522a-7563-92fe-adbf81950a9e" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_DocumentFiscalPeriodFocus_019e65e1-522a-7521-a75d-4374ccced835" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_DocumentFiscalPeriodFocus"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_DocumentFiscalPeriodFocus_019e65e1-522a-7521-a75d-4374ccced835" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityCentralIndexKey_019e65e1-522a-71b1-aec2-957aa263216f" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityCentralIndexKey"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_EntityCentralIndexKey_019e65e1-522a-71b1-aec2-957aa263216f" xlink:type="arc" order="28"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_CurrentFiscalYearEndDate_019e65e1-522a-7634-8a0c-b42be5359436" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_CurrentFiscalYearEndDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_DocumentInformationLineItems_019e65e1-522a-7b92-9058-2f1d58df859c" xlink:to="loc_dei_CurrentFiscalYearEndDate_019e65e1-522a-7634-8a0c-b42be5359436" xlink:type="arc" order="29"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/CondensedBalanceSheetsParenthetical" xlink:type="simple" xlink:href="plrx-20260630.xsd#CondensedBalanceSheetsParenthetical"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/CondensedBalanceSheetsParenthetical" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019e65e1-522a-7387-9df1-6fc248c02ea5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_019e65e1-522a-7f8e-bfe7-c9abe790d0f0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_019e65e1-522a-7387-9df1-6fc248c02ea5" xlink:to="loc_us-gaap_StatementTable_019e65e1-522a-7f8e-bfe7-c9abe790d0f0" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_019e65e1-522a-773e-9fef-fffc60611fdf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019e65e1-522a-7f8e-bfe7-c9abe790d0f0" xlink:to="loc_us-gaap_StatementClassOfStockAxis_019e65e1-522a-773e-9fef-fffc60611fdf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-773e-9fef-fffc60611fdf_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019e65e1-522a-773e-9fef-fffc60611fdf" xlink:to="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-773e-9fef-fffc60611fdf_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-76d9-b89a-1e3a19007c67" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019e65e1-522a-773e-9fef-fffc60611fdf" xlink:to="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-76d9-b89a-1e3a19007c67" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_SeriesAJuniorParticipatingPreferredPurchaseRightsMember_019e65e1-522a-7999-a064-1b12a3ad7f3f" xlink:href="plrx-20260630.xsd#plrx_SeriesAJuniorParticipatingPreferredPurchaseRightsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-76d9-b89a-1e3a19007c67" xlink:to="loc_plrx_SeriesAJuniorParticipatingPreferredPurchaseRightsMember_019e65e1-522a-7999-a064-1b12a3ad7f3f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockParOrStatedValuePerShare_019e65e1-522a-756b-b52b-f3ae870ecbf4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PreferredStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019e65e1-522a-7387-9df1-6fc248c02ea5" xlink:to="loc_us-gaap_PreferredStockParOrStatedValuePerShare_019e65e1-522a-756b-b52b-f3ae870ecbf4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesAuthorized_019e65e1-522a-7f56-a16e-acc4f5592852" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PreferredStockSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019e65e1-522a-7387-9df1-6fc248c02ea5" xlink:to="loc_us-gaap_PreferredStockSharesAuthorized_019e65e1-522a-7f56-a16e-acc4f5592852" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesIssued_019e65e1-522a-7052-8ea9-80d82fa90bfe" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PreferredStockSharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019e65e1-522a-7387-9df1-6fc248c02ea5" xlink:to="loc_us-gaap_PreferredStockSharesIssued_019e65e1-522a-7052-8ea9-80d82fa90bfe" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockSharesOutstanding_019e65e1-522a-76b1-af45-0eaeb57a42bf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PreferredStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019e65e1-522a-7387-9df1-6fc248c02ea5" xlink:to="loc_us-gaap_PreferredStockSharesOutstanding_019e65e1-522a-76b1-af45-0eaeb57a42bf" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockParOrStatedValuePerShare_019e65e1-522a-7bfe-8199-a26947165acd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019e65e1-522a-7387-9df1-6fc248c02ea5" xlink:to="loc_us-gaap_CommonStockParOrStatedValuePerShare_019e65e1-522a-7bfe-8199-a26947165acd" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesAuthorized_019e65e1-522a-7b4a-9dd0-e77e31007175" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019e65e1-522a-7387-9df1-6fc248c02ea5" xlink:to="loc_us-gaap_CommonStockSharesAuthorized_019e65e1-522a-7b4a-9dd0-e77e31007175" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesIssued_019e65e1-522a-79b8-b479-ab9a13c53d23" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockSharesIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019e65e1-522a-7387-9df1-6fc248c02ea5" xlink:to="loc_us-gaap_CommonStockSharesIssued_019e65e1-522a-79b8-b479-ab9a13c53d23" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_019e65e1-522a-70e4-a5a4-c481aa884aab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019e65e1-522a-7387-9df1-6fc248c02ea5" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_019e65e1-522a-70e4-a5a4-c481aa884aab" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/CondensedStatementsofStockholdersEquity" xlink:type="simple" xlink:href="plrx-20260630.xsd#CondensedStatementsofStockholdersEquity"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/CondensedStatementsofStockholdersEquity" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_019e65e1-522a-75eb-bd0a-b8c36b4ad30a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_019e65e1-522a-7dab-9fc5-d9df981691f5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_019e65e1-522a-75eb-bd0a-b8c36b4ad30a" xlink:to="loc_us-gaap_StatementTable_019e65e1-522a-7dab-9fc5-d9df981691f5" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_019e65e1-522a-7566-b0de-d4cf355bf75d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_019e65e1-522a-7dab-9fc5-d9df981691f5" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_019e65e1-522a-7566-b0de-d4cf355bf75d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019e65e1-522a-7566-b0de-d4cf355bf75d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019e65e1-522a-7566-b0de-d4cf355bf75d" xlink:to="loc_us-gaap_EquityComponentDomain_019e65e1-522a-7566-b0de-d4cf355bf75d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_019e65e1-522a-75cf-80f5-f3faf1b5989b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_019e65e1-522a-7566-b0de-d4cf355bf75d" xlink:to="loc_us-gaap_EquityComponentDomain_019e65e1-522a-75cf-80f5-f3faf1b5989b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_019e65e1-522a-7b02-896a-fbccc79aab4d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019e65e1-522a-75cf-80f5-f3faf1b5989b" xlink:to="loc_us-gaap_CommonStockMember_019e65e1-522a-7b02-896a-fbccc79aab4d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_019e65e1-522a-73ab-82c5-c4bb976b70b8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019e65e1-522a-75cf-80f5-f3faf1b5989b" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_019e65e1-522a-73ab-82c5-c4bb976b70b8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019e65e1-522a-7457-a15a-d5b65dab0124" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019e65e1-522a-75cf-80f5-f3faf1b5989b" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_019e65e1-522a-7457-a15a-d5b65dab0124" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_019e65e1-522a-7095-9616-b353e25f0c51" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_019e65e1-522a-75cf-80f5-f3faf1b5989b" xlink:to="loc_us-gaap_RetainedEarningsMember_019e65e1-522a-7095-9616-b353e25f0c51" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e65e1-522a-7ccf-a016-01af662b8104" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_019e65e1-522a-75eb-bd0a-b8c36b4ad30a" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e65e1-522a-7ccf-a016-01af662b8104" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_019e65e1-522a-7cac-b4e3-a5c1f3f38a5c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e65e1-522a-7ccf-a016-01af662b8104" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_019e65e1-522a-7cac-b4e3-a5c1f3f38a5c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019e65e1-522a-7078-9d8d-75cf66acea21" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e65e1-522a-7ccf-a016-01af662b8104" xlink:to="loc_us-gaap_StockholdersEquity_019e65e1-522a-7078-9d8d-75cf66acea21" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeBenefitPlan_019e65e1-522a-747b-acb2-c43e1d586c01" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodSharesEmployeeBenefitPlan"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e65e1-522a-7ccf-a016-01af662b8104" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesEmployeeBenefitPlan_019e65e1-522a-747b-acb2-c43e1d586c01" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeBenefitPlan_019e65e1-522a-782c-858c-2ff2460f28e0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodValueEmployeeBenefitPlan"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e65e1-522a-7ccf-a016-01af662b8104" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueEmployeeBenefitPlan_019e65e1-522a-782c-858c-2ff2460f28e0" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_019e65e1-522a-7263-aac6-9a248674ea61" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e65e1-522a-7ccf-a016-01af662b8104" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_019e65e1-522a-7263-aac6-9a248674ea61" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_019e65e1-522a-7371-8081-7c6922d73144" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e65e1-522a-7ccf-a016-01af662b8104" xlink:to="loc_us-gaap_OtherComprehensiveIncomeUnrealizedHoldingGainLossOnSecuritiesArisingDuringPeriodNetOfTax_019e65e1-522a-7371-8081-7c6922d73144" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019e65e1-522a-7736-92ff-970f1c2f7262" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_019e65e1-522a-7ccf-a016-01af662b8104" xlink:to="loc_us-gaap_NetIncomeLoss_019e65e1-522a-7736-92ff-970f1c2f7262" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_019e65e1-522a-7bfa-be1d-800e215fe335" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_019e65e1-522a-7712-95b5-5cc623852302" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/FinancialInstrumentsNarrativeDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#FinancialInstrumentsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/FinancialInstrumentsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueBalanceSheetGroupingFinancialStatementCaptionsLineItems_019e65e1-522a-7591-a667-b0b23c7f86e4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueBalanceSheetGroupingFinancialStatementCaptionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByBalanceSheetGroupingTable_019e65e1-522a-7352-b2e0-99e32f789db1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueByBalanceSheetGroupingTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueBalanceSheetGroupingFinancialStatementCaptionsLineItems_019e65e1-522a-7591-a667-b0b23c7f86e4" xlink:to="loc_us-gaap_FairValueByBalanceSheetGroupingTable_019e65e1-522a-7352-b2e0-99e32f789db1" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019e65e1-522a-72e9-82d0-7e8143e9a7d5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueByBalanceSheetGroupingTable_019e65e1-522a-7352-b2e0-99e32f789db1" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019e65e1-522a-72e9-82d0-7e8143e9a7d5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e65e1-522a-72e9-82d0-7e8143e9a7d5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019e65e1-522a-72e9-82d0-7e8143e9a7d5" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e65e1-522a-72e9-82d0-7e8143e9a7d5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e65e1-522a-77a5-91f6-57f2d82d0969" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019e65e1-522a-72e9-82d0-7e8143e9a7d5" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e65e1-522a-77a5-91f6-57f2d82d0969" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_019e65e1-522a-7a05-b9da-6e04fc441002" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e65e1-522a-77a5-91f6-57f2d82d0969" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_019e65e1-522a-7a05-b9da-6e04fc441002" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementFrequencyAxis_019e65e1-522a-76e9-851d-bc10b6323d7c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueByMeasurementFrequencyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueByBalanceSheetGroupingTable_019e65e1-522a-7352-b2e0-99e32f789db1" xlink:to="loc_us-gaap_FairValueByMeasurementFrequencyAxis_019e65e1-522a-76e9-851d-bc10b6323d7c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_019e65e1-522a-76e9-851d-bc10b6323d7c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_019e65e1-522a-76e9-851d-bc10b6323d7c" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_019e65e1-522a-76e9-851d-bc10b6323d7c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementFrequencyDomain_019e65e1-522a-7711-8bc0-10592c2e2ee6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementFrequencyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementFrequencyAxis_019e65e1-522a-76e9-851d-bc10b6323d7c" xlink:to="loc_us-gaap_FairValueMeasurementFrequencyDomain_019e65e1-522a-7711-8bc0-10592c2e2ee6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsRecurringMember_019e65e1-522a-7b5e-afe4-9b003c9c1637" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsRecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_019e65e1-522a-7711-8bc0-10592c2e2ee6" xlink:to="loc_us-gaap_FairValueMeasurementsRecurringMember_019e65e1-522a-7b5e-afe4-9b003c9c1637" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsNonrecurringMember_019e65e1-522a-7fc2-ad03-b2ef469d5731" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsNonrecurringMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementFrequencyDomain_019e65e1-522a-7711-8bc0-10592c2e2ee6" xlink:to="loc_us-gaap_FairValueMeasurementsNonrecurringMember_019e65e1-522a-7fc2-ad03-b2ef469d5731" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_019e65e1-522a-7b8b-ae31-d3a781dbe2ab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueBalanceSheetGroupingFinancialStatementCaptionsLineItems_019e65e1-522a-7591-a667-b0b23c7f86e4" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_019e65e1-522a-7b8b-ae31-d3a781dbe2ab" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialLiabilitiesFairValueDisclosure_019e65e1-522a-7b10-840e-e8e0147d320f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinancialLiabilitiesFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueBalanceSheetGroupingFinancialStatementCaptionsLineItems_019e65e1-522a-7591-a667-b0b23c7f86e4" xlink:to="loc_us-gaap_FinancialLiabilitiesFairValueDisclosure_019e65e1-522a-7b10-840e-e8e0147d320f" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/FinancialInstrumentsScheduleofCashandCashEquivalentsMoneyMarketFundsandShorttermInvestmentsbySignificantInvestmentCategoryDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#FinancialInstrumentsScheduleofCashandCashEquivalentsMoneyMarketFundsandShorttermInvestmentsbySignificantInvestmentCategoryDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/FinancialInstrumentsScheduleofCashandCashEquivalentsMoneyMarketFundsandShorttermInvestmentsbySignificantInvestmentCategoryDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019e65e1-522a-7eb5-afca-b055599cb7ca" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019e65e1-522a-7937-8e9a-b565c0d3c855" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019e65e1-522a-7eb5-afca-b055599cb7ca" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019e65e1-522a-7937-8e9a-b565c0d3c855" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019e65e1-522a-7db1-a793-f3d2977d2724" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019e65e1-522a-7937-8e9a-b565c0d3c855" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019e65e1-522a-7db1-a793-f3d2977d2724" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e65e1-522a-7db1-a793-f3d2977d2724_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019e65e1-522a-7db1-a793-f3d2977d2724" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e65e1-522a-7db1-a793-f3d2977d2724_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e65e1-522a-7e21-b4ae-ee32025ffafa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_019e65e1-522a-7db1-a793-f3d2977d2724" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e65e1-522a-7e21-b4ae-ee32025ffafa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_019e65e1-522a-788f-98a0-4e769ee86399" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e65e1-522a-7e21-b4ae-ee32025ffafa" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_019e65e1-522a-788f-98a0-4e769ee86399" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_019e65e1-522a-724a-b1c7-dd2472ebac70" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_019e65e1-522a-7e21-b4ae-ee32025ffafa" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_019e65e1-522a-724a-b1c7-dd2472ebac70" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAndCashEquivalentsAxis_019e65e1-522a-7647-b67b-1be13b91996f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashAndCashEquivalentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019e65e1-522a-7937-8e9a-b565c0d3c855" xlink:to="loc_us-gaap_CashAndCashEquivalentsAxis_019e65e1-522a-7647-b67b-1be13b91996f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019e65e1-522a-7647-b67b-1be13b91996f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CashAndCashEquivalentsAxis_019e65e1-522a-7647-b67b-1be13b91996f" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019e65e1-522a-7647-b67b-1be13b91996f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019e65e1-522a-77a6-b07c-964b95891607" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CashAndCashEquivalentsAxis_019e65e1-522a-7647-b67b-1be13b91996f" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019e65e1-522a-77a6-b07c-964b95891607" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashEquivalentsMember_019e65e1-522a-7dbd-a395-71daa4694ea6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_019e65e1-522a-77a6-b07c-964b95891607" xlink:to="loc_us-gaap_CashEquivalentsMember_019e65e1-522a-7dbd-a395-71daa4694ea6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MoneyMarketFundsMember_019e65e1-522a-7149-9a04-782b4354e19b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MoneyMarketFundsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CashEquivalentsMember_019e65e1-522a-7dbd-a395-71daa4694ea6" xlink:to="loc_us-gaap_MoneyMarketFundsMember_019e65e1-522a-7149-9a04-782b4354e19b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_019e65e1-522a-7b91-8498-b80ed2c055d4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_019e65e1-522a-7937-8e9a-b565c0d3c855" xlink:to="loc_us-gaap_FinancialInstrumentAxis_019e65e1-522a-7b91-8498-b80ed2c055d4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019e65e1-522a-7b91-8498-b80ed2c055d4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019e65e1-522a-7b91-8498-b80ed2c055d4" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019e65e1-522a-7b91-8498-b80ed2c055d4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019e65e1-522a-7626-9b4e-df1d2fadd88f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_019e65e1-522a-7b91-8498-b80ed2c055d4" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019e65e1-522a-7626-9b4e-df1d2fadd88f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermInvestmentsMember_019e65e1-522a-7df9-ad27-f43a80c9aa58" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShortTermInvestmentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_019e65e1-522a-7626-9b4e-df1d2fadd88f" xlink:to="loc_us-gaap_ShortTermInvestmentsMember_019e65e1-522a-7df9-ad27-f43a80c9aa58" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_019e65e1-522a-7978-958b-44a8cedad152" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShortTermInvestmentsMember_019e65e1-522a-7df9-ad27-f43a80c9aa58" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_019e65e1-522a-7978-958b-44a8cedad152" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember_019e65e1-522a-793c-9ca8-8eea853476da" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShortTermInvestmentsMember_019e65e1-522a-7df9-ad27-f43a80c9aa58" xlink:to="loc_us-gaap_USGovernmentCorporationsAndAgenciesSecuritiesMember_019e65e1-522a-793c-9ca8-8eea853476da" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_019e65e1-522a-7595-92f1-01161dc60376" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShortTermInvestmentsMember_019e65e1-522a-7df9-ad27-f43a80c9aa58" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_019e65e1-522a-7595-92f1-01161dc60376" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestBeforeAllowanceForCreditLoss_019e65e1-522a-75a1-aaa4-e05ef7812c52" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestBeforeAllowanceForCreditLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019e65e1-522a-7eb5-afca-b055599cb7ca" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleAmortizedCostExcludingAccruedInterestBeforeAllowanceForCreditLoss_019e65e1-522a-75a1-aaa4-e05ef7812c52" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019e65e1-522a-7a39-b793-dca5418e0902" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019e65e1-522a-7eb5-afca-b055599cb7ca" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_019e65e1-522a-7a39-b793-dca5418e0902" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019e65e1-522a-78c6-b8f7-d0dc13ad545e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019e65e1-522a-7eb5-afca-b055599cb7ca" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_019e65e1-522a-78c6-b8f7-d0dc13ad545e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterest_019e65e1-522a-73bc-bf77-197c3b68ba67" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_019e65e1-522a-7eb5-afca-b055599cb7ca" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleExcludingAccruedInterest_019e65e1-522a-73bc-bf77-197c3b68ba67" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/PropertyandEquipmentnetScheduleofPropertyandEquipmentNetDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#PropertyandEquipmentnetScheduleofPropertyandEquipmentNetDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/PropertyandEquipmentnetScheduleofPropertyandEquipmentNetDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e65e1-522a-7e1e-b6fc-5ac9507aff51" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_019e65e1-522a-77f8-b110-4d0b6d4a0908" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e65e1-522a-7e1e-b6fc-5ac9507aff51" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_019e65e1-522a-77f8-b110-4d0b6d4a0908" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019e65e1-522a-7004-ba77-89066e838607" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_019e65e1-522a-77f8-b110-4d0b6d4a0908" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019e65e1-522a-7004-ba77-89066e838607" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-7004-ba77-89066e838607_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019e65e1-522a-7004-ba77-89066e838607" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-7004-ba77-89066e838607_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-77bf-a165-b19a78dd1e0d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019e65e1-522a-7004-ba77-89066e838607" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-77bf-a165-b19a78dd1e0d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquipmentMember_019e65e1-522a-7d4e-8491-c5bf173278e2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-77bf-a165-b19a78dd1e0d" xlink:to="loc_us-gaap_EquipmentMember_019e65e1-522a-7d4e-8491-c5bf173278e2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LeaseholdImprovementsMember_019e65e1-522a-7e9e-abdb-7b776e9cdb82" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LeaseholdImprovementsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-77bf-a165-b19a78dd1e0d" xlink:to="loc_us-gaap_LeaseholdImprovementsMember_019e65e1-522a-7e9e-abdb-7b776e9cdb82" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FurnitureAndFixturesMember_019e65e1-522a-7ebe-8228-b2cb0c8a6d54" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FurnitureAndFixturesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-77bf-a165-b19a78dd1e0d" xlink:to="loc_us-gaap_FurnitureAndFixturesMember_019e65e1-522a-7ebe-8228-b2cb0c8a6d54" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_ComputerEquipmentAndSoftwareMember_019e65e1-522a-71c9-a34b-3090150ca33b" xlink:href="plrx-20260630.xsd#plrx_ComputerEquipmentAndSoftwareMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-77bf-a165-b19a78dd1e0d" xlink:to="loc_plrx_ComputerEquipmentAndSoftwareMember_019e65e1-522a-71c9-a34b-3090150ca33b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConstructionInProgressMember_019e65e1-522a-78cb-b5b0-ba8bf929a364" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConstructionInProgressMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-77bf-a165-b19a78dd1e0d" xlink:to="loc_us-gaap_ConstructionInProgressMember_019e65e1-522a-78cb-b5b0-ba8bf929a364" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentGross_019e65e1-522a-743a-bce9-816c486ea1b0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e65e1-522a-7e1e-b6fc-5ac9507aff51" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentGross_019e65e1-522a-743a-bce9-816c486ea1b0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_019e65e1-522a-7eb6-8d41-3f7d65676dec" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e65e1-522a-7e1e-b6fc-5ac9507aff51" xlink:to="loc_us-gaap_AccumulatedDepreciationDepletionAndAmortizationPropertyPlantAndEquipment_019e65e1-522a-7eb6-8d41-3f7d65676dec" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentNet_019e65e1-522a-7b2e-b939-85f35f4b4e1c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e65e1-522a-7e1e-b6fc-5ac9507aff51" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentNet_019e65e1-522a-7b2e-b939-85f35f4b4e1c" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/PropertyandEquipmentnetScheduleofAssetsHeldforSaleDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#PropertyandEquipmentnetScheduleofAssetsHeldforSaleDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/PropertyandEquipmentnetScheduleofAssetsHeldforSaleDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e65e1-522a-7424-b40b-0b4aca5000d1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_019e65e1-522a-7272-9fc3-0a47a4442a0d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e65e1-522a-7424-b40b-0b4aca5000d1" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_019e65e1-522a-7272-9fc3-0a47a4442a0d" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019e65e1-522a-7297-99a0-a758c57c8c6b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_019e65e1-522a-7272-9fc3-0a47a4442a0d" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019e65e1-522a-7297-99a0-a758c57c8c6b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-7297-99a0-a758c57c8c6b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019e65e1-522a-7297-99a0-a758c57c8c6b" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-7297-99a0-a758c57c8c6b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-7758-bb22-48a51809ac73" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentByTypeAxis_019e65e1-522a-7297-99a0-a758c57c8c6b" xlink:to="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-7758-bb22-48a51809ac73" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquipmentMember_019e65e1-522a-79f7-9eb8-5d823e4c953a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquipmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentTypeDomain_019e65e1-522a-7758-bb22-48a51809ac73" xlink:to="loc_us-gaap_EquipmentMember_019e65e1-522a-79f7-9eb8-5d823e4c953a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisposalGroupIncludingDiscontinuedOperationPropertyPlantAndEquipment_019e65e1-522a-701c-8117-17781c2ef757" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisposalGroupIncludingDiscontinuedOperationPropertyPlantAndEquipment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_019e65e1-522a-7424-b40b-0b4aca5000d1" xlink:to="loc_us-gaap_DisposalGroupIncludingDiscontinuedOperationPropertyPlantAndEquipment_019e65e1-522a-701c-8117-17781c2ef757" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/AccruedLiabilitiesNarrativeDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#AccruedLiabilitiesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/AccruedLiabilitiesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherSignificantNoncashTransactionsLineItems_019e65e1-522a-78b4-a83a-3fef4d44872a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherSignificantNoncashTransactionsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherSignificantNoncashTransactionsTable_019e65e1-522a-7d3d-8552-e9c2ee437c07" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherSignificantNoncashTransactionsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_OtherSignificantNoncashTransactionsLineItems_019e65e1-522a-78b4-a83a-3fef4d44872a" xlink:to="loc_us-gaap_OtherSignificantNoncashTransactionsTable_019e65e1-522a-7d3d-8552-e9c2ee437c07" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringCostAndReserveAxis_019e65e1-522a-7208-96eb-073eed990829" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringCostAndReserveAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_OtherSignificantNoncashTransactionsTable_019e65e1-522a-7d3d-8552-e9c2ee437c07" xlink:to="loc_us-gaap_RestructuringCostAndReserveAxis_019e65e1-522a-7208-96eb-073eed990829" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfRestructuringDomain_019e65e1-522a-7208-96eb-073eed990829_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TypeOfRestructuringDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestructuringCostAndReserveAxis_019e65e1-522a-7208-96eb-073eed990829" xlink:to="loc_us-gaap_TypeOfRestructuringDomain_019e65e1-522a-7208-96eb-073eed990829_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TypeOfRestructuringDomain_019e65e1-522a-7a1a-aa13-e450356eba69" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TypeOfRestructuringDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestructuringCostAndReserveAxis_019e65e1-522a-7208-96eb-073eed990829" xlink:to="loc_us-gaap_TypeOfRestructuringDomain_019e65e1-522a-7a1a-aa13-e450356eba69" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeSeveranceMember_019e65e1-522a-71c2-9a83-2771bce8615f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeSeveranceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TypeOfRestructuringDomain_019e65e1-522a-7a1a-aa13-e450356eba69" xlink:to="loc_us-gaap_EmployeeSeveranceMember_019e65e1-522a-71c2-9a83-2771bce8615f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestructuringReserve_019e65e1-522a-75b5-8ce0-488ed0d3e271" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestructuringReserve"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherSignificantNoncashTransactionsLineItems_019e65e1-522a-78b4-a83a-3fef4d44872a" xlink:to="loc_us-gaap_RestructuringReserve_019e65e1-522a-75b5-8ce0-488ed0d3e271" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/LongtermDebtDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#LongtermDebtDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/LongtermDebtDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_019e65e1-522a-7f85-8d6e-f2cd0a499113" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_019e65e1-522a-7c8e-966e-9b415c4bdde7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_019e65e1-522a-7f85-8d6e-f2cd0a499113" xlink:to="loc_us-gaap_DebtInstrumentTable_019e65e1-522a-7c8e-966e-9b415c4bdde7" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_019e65e1-522a-7043-a2ad-1e4cac623857" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_019e65e1-522a-7c8e-966e-9b415c4bdde7" xlink:to="loc_us-gaap_DebtInstrumentAxis_019e65e1-522a-7043-a2ad-1e4cac623857" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_019e65e1-522a-7043-a2ad-1e4cac623857_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_019e65e1-522a-7043-a2ad-1e4cac623857" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_019e65e1-522a-7043-a2ad-1e4cac623857_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_019e65e1-522a-76ca-b0ca-4ad5b4c5a70e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_019e65e1-522a-7043-a2ad-1e4cac623857" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_019e65e1-522a-76ca-b0ca-4ad5b4c5a70e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_LoanAgreementMember_019e65e1-522a-78af-bd15-1a8426dfff6d" xlink:href="plrx-20260630.xsd#plrx_LoanAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_019e65e1-522a-76ca-b0ca-4ad5b4c5a70e" xlink:to="loc_plrx_LoanAgreementMember_019e65e1-522a-78af-bd15-1a8426dfff6d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_019e65e1-522a-7fe7-9c18-7a8bb4779afa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_019e65e1-522a-7c8e-966e-9b415c4bdde7" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_019e65e1-522a-7fe7-9c18-7a8bb4779afa" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_019e65e1-522a-7fe7-9c18-7a8bb4779afa_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_019e65e1-522a-7fe7-9c18-7a8bb4779afa" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_019e65e1-522a-7fe7-9c18-7a8bb4779afa_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_019e65e1-522a-7f68-98db-f91ccef05aaa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_019e65e1-522a-7fe7-9c18-7a8bb4779afa" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_019e65e1-522a-7f68-98db-f91ccef05aaa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_TermLoanFacilityMember_019e65e1-522a-7218-bec1-7a854b610f00" xlink:href="plrx-20260630.xsd#plrx_TermLoanFacilityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_019e65e1-522a-7f68-98db-f91ccef05aaa" xlink:to="loc_plrx_TermLoanFacilityMember_019e65e1-522a-7218-bec1-7a854b610f00" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFaceAmount_019e65e1-522a-7677-8186-7e493c3c6423" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentFaceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_019e65e1-522a-7f85-8d6e-f2cd0a499113" xlink:to="loc_us-gaap_DebtInstrumentFaceAmount_019e65e1-522a-7677-8186-7e493c3c6423" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromLinesOfCredit_019e65e1-522a-7ba4-b74e-6eb775f7c8c7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProceedsFromLinesOfCredit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_019e65e1-522a-7f85-8d6e-f2cd0a499113" xlink:to="loc_us-gaap_ProceedsFromLinesOfCredit_019e65e1-522a-7ba4-b74e-6eb775f7c8c7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCredit_019e65e1-522a-7cfe-84b2-95f507961f2a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LineOfCredit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_019e65e1-522a-7f85-8d6e-f2cd0a499113" xlink:to="loc_us-gaap_LineOfCredit_019e65e1-522a-7cfe-84b2-95f507961f2a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfDebt_019e65e1-522a-71c9-ae30-c2858e0f0ae6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RepaymentsOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_019e65e1-522a-7f85-8d6e-f2cd0a499113" xlink:to="loc_us-gaap_RepaymentsOfDebt_019e65e1-522a-71c9-ae30-c2858e0f0ae6" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_019fcd41-0c75-7d18-8c2a-86e8acbe6ddd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_019e65e1-522a-7f85-8d6e-f2cd0a499113" xlink:to="loc_us-gaap_LongTermDebt_019fcd41-0c75-7d18-8c2a-86e8acbe6ddd" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseDebt_019e65e1-522a-7fb1-a0c5-c293a23afa2d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestExpenseDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_019e65e1-522a-7f85-8d6e-f2cd0a499113" xlink:to="loc_us-gaap_InterestExpenseDebt_019e65e1-522a-7fb1-a0c5-c293a23afa2d" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/CommonStockScheduleofSharesReservedforFutureIssuanceDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#CommonStockScheduleofSharesReservedforFutureIssuanceDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/CommonStockScheduleofSharesReservedforFutureIssuanceDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_019e65e1-522a-7b7d-a52b-3b763039b084" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_019e65e1-522a-7eb8-bd82-c038e6a2d436" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_019e65e1-522a-7b7d-a52b-3b763039b084" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_019e65e1-522a-7eb8-bd82-c038e6a2d436" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7b35-b64a-fedddfbb3019" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_019e65e1-522a-7eb8-bd82-c038e6a2d436" xlink:to="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7b35-b64a-fedddfbb3019" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7b35-b64a-fedddfbb3019_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7b35-b64a-fedddfbb3019" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7b35-b64a-fedddfbb3019_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7089-add4-61876a98d4e9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7b35-b64a-fedddfbb3019" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7089-add4-61876a98d4e9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_019e65e1-522a-7d96-b640-aea9a80f8adf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7089-add4-61876a98d4e9" xlink:to="loc_us-gaap_EmployeeStockOptionMember_019e65e1-522a-7d96-b640-aea9a80f8adf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019e65e1-522a-711f-8e08-882aab469351" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7089-add4-61876a98d4e9" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019e65e1-522a-711f-8e08-882aab469351" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_019e65e1-522a-7fc1-91ed-5589c49bca5c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_019e65e1-522a-7eb8-bd82-c038e6a2d436" xlink:to="loc_us-gaap_PlanNameAxis_019e65e1-522a-7fc1-91ed-5589c49bca5c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e65e1-522a-7fc1-91ed-5589c49bca5c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_019e65e1-522a-7fc1-91ed-5589c49bca5c" xlink:to="loc_us-gaap_PlanNameDomain_019e65e1-522a-7fc1-91ed-5589c49bca5c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e65e1-522a-7543-92de-05b8465a4f85" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_019e65e1-522a-7fc1-91ed-5589c49bca5c" xlink:to="loc_us-gaap_PlanNameDomain_019e65e1-522a-7543-92de-05b8465a4f85" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_TwoThousandAndTwentyStockOptionsAndIncentivePlanMember_019e65e1-522a-7b85-aee7-ff1c8275c856" xlink:href="plrx-20260630.xsd#plrx_TwoThousandAndTwentyStockOptionsAndIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019e65e1-522a-7543-92de-05b8465a4f85" xlink:to="loc_plrx_TwoThousandAndTwentyStockOptionsAndIncentivePlanMember_019e65e1-522a-7b85-aee7-ff1c8275c856" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_TwoThousandAndTwentyEmployeeStockPurchasePlanMember_019e65e1-522a-7c05-95c6-2aad7da24017" xlink:href="plrx-20260630.xsd#plrx_TwoThousandAndTwentyEmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019e65e1-522a-7543-92de-05b8465a4f85" xlink:to="loc_plrx_TwoThousandAndTwentyEmployeeStockPurchasePlanMember_019e65e1-522a-7c05-95c6-2aad7da24017" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_TwoThousandAndTwentyTwoInducementPlanMember_019e65e1-522a-76ff-8f39-f240bbc17b87" xlink:href="plrx-20260630.xsd#plrx_TwoThousandAndTwentyTwoInducementPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019e65e1-522a-7543-92de-05b8465a4f85" xlink:to="loc_plrx_TwoThousandAndTwentyTwoInducementPlanMember_019e65e1-522a-76ff-8f39-f240bbc17b87" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_019e65e1-522a-76c4-ba3c-b3943d2fc1c0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_019e65e1-522a-7b7d-a52b-3b763039b084" xlink:to="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_019e65e1-522a-76c4-ba3c-b3943d2fc1c0" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/StockholderRightsAgreementDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#StockholderRightsAgreementDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/StockholderRightsAgreementDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e65e1-522a-746d-bdf0-bbcaccedd88c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightTable_019e65e1-522a-724b-ac06-2473c17ffca2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e65e1-522a-746d-bdf0-bbcaccedd88c" xlink:to="loc_us-gaap_ClassOfWarrantOrRightTable_019e65e1-522a-724b-ac06-2473c17ffca2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightAxis_019e65e1-522a-7108-ad52-c2e4ce8173bd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ClassOfWarrantOrRightTable_019e65e1-522a-724b-ac06-2473c17ffca2" xlink:to="loc_us-gaap_ClassOfWarrantOrRightAxis_019e65e1-522a-7108-ad52-c2e4ce8173bd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_019e65e1-522a-7108-ad52-c2e4ce8173bd_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_019e65e1-522a-7108-ad52-c2e4ce8173bd" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_019e65e1-522a-7108-ad52-c2e4ce8173bd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_019e65e1-522a-7a27-adcd-e236fb380cb2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_019e65e1-522a-7108-ad52-c2e4ce8173bd" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_019e65e1-522a-7a27-adcd-e236fb380cb2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_RightsAgreementMember_019e65e1-522a-76b3-b221-bb4938d7aeb3" xlink:href="plrx-20260630.xsd#plrx_RightsAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_019e65e1-522a-7a27-adcd-e236fb380cb2" xlink:to="loc_plrx_RightsAgreementMember_019e65e1-522a-76b3-b221-bb4938d7aeb3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_019e65e1-522a-7934-b1ef-99941ce2e70a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ClassOfWarrantOrRightTable_019e65e1-522a-724b-ac06-2473c17ffca2" xlink:to="loc_us-gaap_StatementClassOfStockAxis_019e65e1-522a-7934-b1ef-99941ce2e70a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-7934-b1ef-99941ce2e70a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019e65e1-522a-7934-b1ef-99941ce2e70a" xlink:to="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-7934-b1ef-99941ce2e70a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-77d7-943e-87d4c3ed2c85" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_019e65e1-522a-7934-b1ef-99941ce2e70a" xlink:to="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-77d7-943e-87d4c3ed2c85" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_SeriesAJuniorParticipatingPreferredPurchaseRightsMember_019e65e1-522a-78b4-b86b-c4e11344db17" xlink:href="plrx-20260630.xsd#plrx_SeriesAJuniorParticipatingPreferredPurchaseRightsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_019e65e1-522a-77d7-943e-87d4c3ed2c85" xlink:to="loc_plrx_SeriesAJuniorParticipatingPreferredPurchaseRightsMember_019e65e1-522a-78b4-b86b-c4e11344db17" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_DividendDistributionNumberOfRightsDeclared_019e65e1-522a-78bf-910f-cbced39065d0" xlink:href="plrx-20260630.xsd#plrx_DividendDistributionNumberOfRightsDeclared"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e65e1-522a-746d-bdf0-bbcaccedd88c" xlink:to="loc_plrx_DividendDistributionNumberOfRightsDeclared_019e65e1-522a-78bf-910f-cbced39065d0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_NumberOfSharesPerRightEntitledToPurchase_019e65e1-522a-7a7a-99bd-edd151cc4afc" xlink:href="plrx-20260630.xsd#plrx_NumberOfSharesPerRightEntitledToPurchase"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e65e1-522a-746d-bdf0-bbcaccedd88c" xlink:to="loc_plrx_NumberOfSharesPerRightEntitledToPurchase_019e65e1-522a-7a7a-99bd-edd151cc4afc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockParOrStatedValuePerShare_019e65e1-522a-7992-80ec-738e8059ca8e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PreferredStockParOrStatedValuePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e65e1-522a-746d-bdf0-bbcaccedd88c" xlink:to="loc_us-gaap_PreferredStockParOrStatedValuePerShare_019e65e1-522a-7992-80ec-738e8059ca8e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_019e65e1-522a-7373-8865-caf9547e478b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e65e1-522a-746d-bdf0-bbcaccedd88c" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_019e65e1-522a-7373-8865-caf9547e478b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_ClassOfWarrantOrRightExercisableAfterBeneficialOwnershipThresholdAnnouncementNumberOfDays_019e65e1-522a-784e-bbe6-904268937737" xlink:href="plrx-20260630.xsd#plrx_ClassOfWarrantOrRightExercisableAfterBeneficialOwnershipThresholdAnnouncementNumberOfDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e65e1-522a-746d-bdf0-bbcaccedd88c" xlink:to="loc_plrx_ClassOfWarrantOrRightExercisableAfterBeneficialOwnershipThresholdAnnouncementNumberOfDays_019e65e1-522a-784e-bbe6-904268937737" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_ClassOfWarrantOrRightAcquiringPersonsBeneficialOwnershipThresholdPassiveInvestor_019e65e1-522a-72ed-b2c0-f9e89fb5c221" xlink:href="plrx-20260630.xsd#plrx_ClassOfWarrantOrRightAcquiringPersonsBeneficialOwnershipThresholdPassiveInvestor"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e65e1-522a-746d-bdf0-bbcaccedd88c" xlink:to="loc_plrx_ClassOfWarrantOrRightAcquiringPersonsBeneficialOwnershipThresholdPassiveInvestor_019e65e1-522a-72ed-b2c0-f9e89fb5c221" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_ClassOfWarrantOrRightAcquiringPersonsBeneficialOwnershipThresholdNonPassiveInvestor_019e65e1-522a-7aec-9b63-7156bf2f1283" xlink:href="plrx-20260630.xsd#plrx_ClassOfWarrantOrRightAcquiringPersonsBeneficialOwnershipThresholdNonPassiveInvestor"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e65e1-522a-746d-bdf0-bbcaccedd88c" xlink:to="loc_plrx_ClassOfWarrantOrRightAcquiringPersonsBeneficialOwnershipThresholdNonPassiveInvestor_019e65e1-522a-7aec-9b63-7156bf2f1283" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_019e65e1-522a-72ef-a83a-6fc53458000f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightLineItems_019e65e1-522a-746d-bdf0-bbcaccedd88c" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_019e65e1-522a-72ef-a83a-6fc53458000f" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationEquityIncentivePlanNarrativeDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#EquityIncentivePlansandStockBasedCompensationEquityIncentivePlanNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationEquityIncentivePlanNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7493-b89b-7a21ca29aab4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7c4f-b89a-c42067e2f95e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7493-b89b-7a21ca29aab4" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7c4f-b89a-c42067e2f95e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_019e65e1-522a-7412-aca0-5d686fd1b926" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7c4f-b89a-c42067e2f95e" xlink:to="loc_srt_RangeAxis_019e65e1-522a-7412-aca0-5d686fd1b926" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019e65e1-522a-7412-aca0-5d686fd1b926_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_019e65e1-522a-7412-aca0-5d686fd1b926" xlink:to="loc_srt_RangeMember_019e65e1-522a-7412-aca0-5d686fd1b926_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019e65e1-522a-7f3e-99df-87540f17f456" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_019e65e1-522a-7412-aca0-5d686fd1b926" xlink:to="loc_srt_RangeMember_019e65e1-522a-7f3e-99df-87540f17f456" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_019e65e1-522a-72de-989c-ce6f5da0a968" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019e65e1-522a-7f3e-99df-87540f17f456" xlink:to="loc_srt_MaximumMember_019e65e1-522a-72de-989c-ce6f5da0a968" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_019e65e1-522a-788e-a115-1caa94d14d57" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7c4f-b89a-c42067e2f95e" xlink:to="loc_us-gaap_PlanNameAxis_019e65e1-522a-788e-a115-1caa94d14d57" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e65e1-522a-788e-a115-1caa94d14d57_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_019e65e1-522a-788e-a115-1caa94d14d57" xlink:to="loc_us-gaap_PlanNameDomain_019e65e1-522a-788e-a115-1caa94d14d57_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e65e1-522a-7997-92ec-0377cd33b430" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_019e65e1-522a-788e-a115-1caa94d14d57" xlink:to="loc_us-gaap_PlanNameDomain_019e65e1-522a-7997-92ec-0377cd33b430" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_TwoThousandAndTwentyStockOptionsAndIncentivePlanAndTwoThousandTwentyTwoInducementPlanMember_019e65e1-522a-7610-b41f-0a9a97e12f8f" xlink:href="plrx-20260630.xsd#plrx_TwoThousandAndTwentyStockOptionsAndIncentivePlanAndTwoThousandTwentyTwoInducementPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019e65e1-522a-7997-92ec-0377cd33b430" xlink:to="loc_plrx_TwoThousandAndTwentyStockOptionsAndIncentivePlanAndTwoThousandTwentyTwoInducementPlanMember_019e65e1-522a-7610-b41f-0a9a97e12f8f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_TwoThousandAndTwentyStockOptionsAndIncentivePlanMember_019e65e1-522a-7953-ab0c-5319a185a0ad" xlink:href="plrx-20260630.xsd#plrx_TwoThousandAndTwentyStockOptionsAndIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_plrx_TwoThousandAndTwentyStockOptionsAndIncentivePlanAndTwoThousandTwentyTwoInducementPlanMember_019e65e1-522a-7610-b41f-0a9a97e12f8f" xlink:to="loc_plrx_TwoThousandAndTwentyStockOptionsAndIncentivePlanMember_019e65e1-522a-7953-ab0c-5319a185a0ad" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_PercentOfOutstandingSharesSharesAddedPerYearToPlan_019e65e1-522a-732e-8146-eac81cabfda0" xlink:href="plrx-20260630.xsd#plrx_PercentOfOutstandingSharesSharesAddedPerYearToPlan"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7493-b89b-7a21ca29aab4" xlink:to="loc_plrx_PercentOfOutstandingSharesSharesAddedPerYearToPlan_019e65e1-522a-732e-8146-eac81cabfda0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_ShareBasedCompensationOptionsUnderPlanMayBeGrantedForPeriods_019e65e1-522a-7ebe-8b0d-8fe6c8674752" xlink:href="plrx-20260630.xsd#plrx_ShareBasedCompensationOptionsUnderPlanMayBeGrantedForPeriods"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7493-b89b-7a21ca29aab4" xlink:to="loc_plrx_ShareBasedCompensationOptionsUnderPlanMayBeGrantedForPeriods_019e65e1-522a-7ebe-8b0d-8fe6c8674752" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardExercisePriceWithPurchasePriceOfCommonStockPercentageOfEstimatedGrantDateFairValueForShareholders_019e65e1-522a-7709-9fe3-72e6f0530035" xlink:href="plrx-20260630.xsd#plrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardExercisePriceWithPurchasePriceOfCommonStockPercentageOfEstimatedGrantDateFairValueForShareholders"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7493-b89b-7a21ca29aab4" xlink:to="loc_plrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardExercisePriceWithPurchasePriceOfCommonStockPercentageOfEstimatedGrantDateFairValueForShareholders_019e65e1-522a-7709-9fe3-72e6f0530035" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_019e65e1-522a-734d-a29f-b287f69f1f4a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7493-b89b-7a21ca29aab4" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_019e65e1-522a-734d-a29f-b287f69f1f4a" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationStockOptionRepricingNarrativeDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#EquityIncentivePlansandStockBasedCompensationStockOptionRepricingNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationStockOptionRepricingNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019edf43-024f-7c74-834c-2105dcea04ce" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019edf43-024f-7761-8a1a-9324f9446521" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019edf43-024f-7c74-834c-2105dcea04ce" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019edf43-024f-7761-8a1a-9324f9446521" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_019edf43-024f-7d17-93f8-ac7f699975f7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019edf43-024f-7761-8a1a-9324f9446521" xlink:to="loc_us-gaap_PlanNameAxis_019edf43-024f-7d17-93f8-ac7f699975f7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019edf43-024f-7d17-93f8-ac7f699975f7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_019edf43-024f-7d17-93f8-ac7f699975f7" xlink:to="loc_us-gaap_PlanNameDomain_019edf43-024f-7d17-93f8-ac7f699975f7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019edf43-024f-7721-b586-b3bca5aa1615" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_019edf43-024f-7d17-93f8-ac7f699975f7" xlink:to="loc_us-gaap_PlanNameDomain_019edf43-024f-7721-b586-b3bca5aa1615" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_TwoThousandFifteenAndTwoThousandTwentyEquityIncentivePlansAndTwoThousandTwentyTwoInducementPlanMember_019edf43-024f-7c72-ad2b-41c50fedb81f" xlink:href="plrx-20260630.xsd#plrx_TwoThousandFifteenAndTwoThousandTwentyEquityIncentivePlansAndTwoThousandTwentyTwoInducementPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019edf43-024f-7721-b586-b3bca5aa1615" xlink:to="loc_plrx_TwoThousandFifteenAndTwoThousandTwentyEquityIncentivePlansAndTwoThousandTwentyTwoInducementPlanMember_019edf43-024f-7c72-ad2b-41c50fedb81f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019edf44-7995-7ee7-9d55-0bd30b5e00a5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019edf43-024f-7761-8a1a-9324f9446521" xlink:to="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019edf44-7995-7ee7-9d55-0bd30b5e00a5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_019edf44-7995-7ee7-9d55-0bd30b5e00a5_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019edf44-7995-7ee7-9d55-0bd30b5e00a5" xlink:to="loc_us-gaap_RelatedPartyDomain_019edf44-7995-7ee7-9d55-0bd30b5e00a5_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_019edf44-7995-78ad-9a29-b844dfd7713f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_019edf44-7995-7ee7-9d55-0bd30b5e00a5" xlink:to="loc_us-gaap_RelatedPartyDomain_019edf44-7995-78ad-9a29-b844dfd7713f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ExecutiveOfficerMember_019edf44-c01b-782b-aaf7-049400cb86ae" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ExecutiveOfficerMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_019edf44-7995-78ad-9a29-b844dfd7713f" xlink:to="loc_srt_ExecutiveOfficerMember_019edf44-c01b-782b-aaf7-049400cb86ae" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_EmployeeMember_019edf46-0fd7-710f-8e79-ce0f8c2b3526" xlink:href="plrx-20260630.xsd#plrx_EmployeeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_019edf44-7995-78ad-9a29-b844dfd7713f" xlink:to="loc_plrx_EmployeeMember_019edf46-0fd7-710f-8e79-ce0f8c2b3526" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019f94c0-b49c-74bb-95fa-37c3d3e82a51" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019edf43-024f-7761-8a1a-9324f9446521" xlink:to="loc_us-gaap_AwardTypeAxis_019f94c0-b49c-74bb-95fa-37c3d3e82a51" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019f94c0-b49c-74bb-95fa-37c3d3e82a51_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019f94c0-b49c-74bb-95fa-37c3d3e82a51" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019f94c0-b49c-74bb-95fa-37c3d3e82a51_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019f94c0-b49c-7f64-8c32-a5221d9fbd9e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019f94c0-b49c-74bb-95fa-37c3d3e82a51" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019f94c0-b49c-7f64-8c32-a5221d9fbd9e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_ShareBasedCompensationArrangementOptionsRepricedMember_019f94c1-1c03-7046-bf73-b53de7b9863c" xlink:href="plrx-20260630.xsd#plrx_ShareBasedCompensationArrangementOptionsRepricedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019f94c0-b49c-7f64-8c32-a5221d9fbd9e" xlink:to="loc_plrx_ShareBasedCompensationArrangementOptionsRepricedMember_019f94c1-1c03-7046-bf73-b53de7b9863c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_019edf43-024f-7b78-9703-18e9a82a3fb8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019edf43-024f-7c74-834c-2105dcea04ce" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_019edf43-024f-7b78-9703-18e9a82a3fb8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_019edf43-cd46-7ee4-98ba-a3bef9aa950b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019edf43-024f-7c74-834c-2105dcea04ce" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_019edf43-cd46-7ee4-98ba-a3bef9aa950b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_019f94c2-c511-72c1-8348-3ea489b5a0f0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019edf43-024f-7c74-834c-2105dcea04ce" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_019f94c2-c511-72c1-8348-3ea489b5a0f0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019f94c0-6096-7ae0-bbd1-cd5464f84328" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019edf43-024f-7c74-834c-2105dcea04ce" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019f94c0-6096-7ae0-bbd1-cd5464f84328" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationIncentiveStockOptionsandNonqualifiedStockOptionsNarrativeDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#EquityIncentivePlansandStockBasedCompensationIncentiveStockOptionsandNonqualifiedStockOptionsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationIncentiveStockOptionsandNonqualifiedStockOptionsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7050-aef5-e4222e53e645" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7083-b1f9-2ec7b7cf2f59" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7050-aef5-e4222e53e645" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7083-b1f9-2ec7b7cf2f59" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_019e65e1-522a-7046-b5b9-7f9636c5d47b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7083-b1f9-2ec7b7cf2f59" xlink:to="loc_us-gaap_PlanNameAxis_019e65e1-522a-7046-b5b9-7f9636c5d47b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e65e1-522a-7046-b5b9-7f9636c5d47b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_019e65e1-522a-7046-b5b9-7f9636c5d47b" xlink:to="loc_us-gaap_PlanNameDomain_019e65e1-522a-7046-b5b9-7f9636c5d47b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e65e1-522a-7b2e-a72d-84c6b232aef1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_019e65e1-522a-7046-b5b9-7f9636c5d47b" xlink:to="loc_us-gaap_PlanNameDomain_019e65e1-522a-7b2e-a72d-84c6b232aef1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_TwoThousandFifteenAndTwoThousandTwentyEquityIncentivePlansAndTwoThousandTwentyTwoInducementPlanMember_019e65e1-522a-7f42-99ff-eddf92969823" xlink:href="plrx-20260630.xsd#plrx_TwoThousandFifteenAndTwoThousandTwentyEquityIncentivePlansAndTwoThousandTwentyTwoInducementPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019e65e1-522a-7b2e-a72d-84c6b232aef1" xlink:to="loc_plrx_TwoThousandFifteenAndTwoThousandTwentyEquityIncentivePlansAndTwoThousandTwentyTwoInducementPlanMember_019e65e1-522a-7f42-99ff-eddf92969823" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7d7e-a4bf-d34ffc2fa99a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7083-b1f9-2ec7b7cf2f59" xlink:to="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7d7e-a4bf-d34ffc2fa99a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7d7e-a4bf-d34ffc2fa99a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7d7e-a4bf-d34ffc2fa99a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7d7e-a4bf-d34ffc2fa99a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7a72-83fa-7ee3d7511fc6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7d7e-a4bf-d34ffc2fa99a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7a72-83fa-7ee3d7511fc6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_IncentiveStockOptionsAndNonqualifiedStockOptionsMember_019e65e1-522a-7b45-b377-5f9d4625b4ba" xlink:href="plrx-20260630.xsd#plrx_IncentiveStockOptionsAndNonqualifiedStockOptionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7a72-83fa-7ee3d7511fc6" xlink:to="loc_plrx_IncentiveStockOptionsAndNonqualifiedStockOptionsMember_019e65e1-522a-7b45-b377-5f9d4625b4ba" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_019e65e1-522a-7505-8361-27d9c70b3269" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7050-aef5-e4222e53e645" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_019e65e1-522a-7505-8361-27d9c70b3269" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_019e65e1-522a-7444-85da-35028ae26809" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7050-aef5-e4222e53e645" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardExpirationPeriod_019e65e1-522a-7444-85da-35028ae26809" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_019e65e1-522a-7292-b75a-08946d19ecdc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7050-aef5-e4222e53e645" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedStockOptions_019e65e1-522a-7292-b75a-08946d19ecdc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019e65e1-522a-718d-9eb0-ef780c3d95df" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7050-aef5-e4222e53e645" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019e65e1-522a-718d-9eb0-ef780c3d95df" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationScheduleofBlackScholesOptionPricingModeltoEstimateStockbasedCompensationExpenseforStockOptionAwardsDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#EquityIncentivePlansandStockBasedCompensationScheduleofBlackScholesOptionPricingModeltoEstimateStockbasedCompensationExpenseforStockOptionAwardsDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationScheduleofBlackScholesOptionPricingModeltoEstimateStockbasedCompensationExpenseforStockOptionAwardsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-78ed-a0b2-b927deaf3a10" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-71d5-86ea-ef938512088c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-78ed-a0b2-b927deaf3a10" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-71d5-86ea-ef938512088c" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7ed2-93dd-a93069beb8a3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-71d5-86ea-ef938512088c" xlink:to="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7ed2-93dd-a93069beb8a3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7ed2-93dd-a93069beb8a3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7ed2-93dd-a93069beb8a3" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7ed2-93dd-a93069beb8a3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-74ae-bb62-86d12ebdaf8e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7ed2-93dd-a93069beb8a3" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-74ae-bb62-86d12ebdaf8e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_IncentiveStockOptionsAndNonqualifiedStockOptionsMember_019e65e1-522a-75ba-bba5-d60e3fb8d701" xlink:href="plrx-20260630.xsd#plrx_IncentiveStockOptionsAndNonqualifiedStockOptionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-74ae-bb62-86d12ebdaf8e" xlink:to="loc_plrx_IncentiveStockOptionsAndNonqualifiedStockOptionsMember_019e65e1-522a-75ba-bba5-d60e3fb8d701" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_019e65e1-522a-721a-aa1a-aafa612b4cb9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-71d5-86ea-ef938512088c" xlink:to="loc_us-gaap_PlanNameAxis_019e65e1-522a-721a-aa1a-aafa612b4cb9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e65e1-522a-721a-aa1a-aafa612b4cb9_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_019e65e1-522a-721a-aa1a-aafa612b4cb9" xlink:to="loc_us-gaap_PlanNameDomain_019e65e1-522a-721a-aa1a-aafa612b4cb9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e65e1-522a-7f68-9d08-2cb83b7e20ef" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_019e65e1-522a-721a-aa1a-aafa612b4cb9" xlink:to="loc_us-gaap_PlanNameDomain_019e65e1-522a-7f68-9d08-2cb83b7e20ef" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_TwoThousandFifteenAndTwoThousandTwentyEquityIncentivePlansAndTwoThousandTwentyTwoInducementPlanMember_019e65e1-522a-78d4-a651-283d87dfe09d" xlink:href="plrx-20260630.xsd#plrx_TwoThousandFifteenAndTwoThousandTwentyEquityIncentivePlansAndTwoThousandTwentyTwoInducementPlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019e65e1-522a-7f68-9d08-2cb83b7e20ef" xlink:to="loc_plrx_TwoThousandFifteenAndTwoThousandTwentyEquityIncentivePlansAndTwoThousandTwentyTwoInducementPlanMember_019e65e1-522a-78d4-a651-283d87dfe09d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_019e65e1-522a-7f5d-9c37-50801fc3a6da" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-71d5-86ea-ef938512088c" xlink:to="loc_srt_RangeAxis_019e65e1-522a-7f5d-9c37-50801fc3a6da" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019e65e1-522a-7f5d-9c37-50801fc3a6da_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_019e65e1-522a-7f5d-9c37-50801fc3a6da" xlink:to="loc_srt_RangeMember_019e65e1-522a-7f5d-9c37-50801fc3a6da_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019e65e1-522a-711c-971f-9127b3513962" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_019e65e1-522a-7f5d-9c37-50801fc3a6da" xlink:to="loc_srt_RangeMember_019e65e1-522a-711c-971f-9127b3513962" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_019e65e1-522a-75ad-9703-507b523cfea2" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019e65e1-522a-711c-971f-9127b3513962" xlink:to="loc_srt_MinimumMember_019e65e1-522a-75ad-9703-507b523cfea2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_019e65e1-522a-76f3-b365-aa9e6cd37d9c" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019e65e1-522a-711c-971f-9127b3513962" xlink:to="loc_srt_MaximumMember_019e65e1-522a-76f3-b365-aa9e6cd37d9c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum_019e65e1-522a-7632-a856-ad983e4e40b2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-78ed-a0b2-b927deaf3a10" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum_019e65e1-522a-7632-a856-ad983e4e40b2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum_019e65e1-522a-70d8-ad43-29c1e260a3bf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-78ed-a0b2-b927deaf3a10" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum_019e65e1-522a-70d8-ad43-29c1e260a3bf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum_019e65e1-522a-7692-83e0-018c5bd3d176" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-78ed-a0b2-b927deaf3a10" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum_019e65e1-522a-7692-83e0-018c5bd3d176" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum_019e65e1-522a-779d-acfd-4f47e6ceef2a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-78ed-a0b2-b927deaf3a10" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum_019e65e1-522a-779d-acfd-4f47e6ceef2a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_019e65e1-522a-71b9-962e-3f6d87ced336" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-78ed-a0b2-b927deaf3a10" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_019e65e1-522a-71b9-962e-3f6d87ced336" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_019e65e1-522a-75c8-a109-ce82ac5071ee" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-78ed-a0b2-b927deaf3a10" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_019e65e1-522a-75c8-a109-ce82ac5071ee" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_UnderlyingCommonStockFairValue_019e65e1-522a-7109-a2ef-86e0b59f96b8" xlink:href="plrx-20260630.xsd#plrx_UnderlyingCommonStockFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-78ed-a0b2-b927deaf3a10" xlink:to="loc_plrx_UnderlyingCommonStockFairValue_019e65e1-522a-7109-a2ef-86e0b59f96b8" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationScheduleofOptionActivityUnderthe2015Planand2020PlanDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#EquityIncentivePlansandStockBasedCompensationScheduleofOptionActivityUnderthe2015Planand2020PlanDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationScheduleofOptionActivityUnderthe2015Planand2020PlanDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-71d9-bec4-ad691bb71e84" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-76ed-aa60-2941ff223ce3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-71d9-bec4-ad691bb71e84" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-76ed-aa60-2941ff223ce3" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019e65e1-522a-77f4-82a2-3e443e07ba4a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-76ed-aa60-2941ff223ce3" xlink:to="loc_us-gaap_AwardTypeAxis_019e65e1-522a-77f4-82a2-3e443e07ba4a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-77f4-82a2-3e443e07ba4a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-77f4-82a2-3e443e07ba4a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-77f4-82a2-3e443e07ba4a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7188-85ea-148514e1f1ab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-77f4-82a2-3e443e07ba4a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7188-85ea-148514e1f1ab" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_IncentiveStockOptionsAndNonqualifiedStockOptionsMember_019e65e1-522a-7bff-bdf9-29186d80a37d" xlink:href="plrx-20260630.xsd#plrx_IncentiveStockOptionsAndNonqualifiedStockOptionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7188-85ea-148514e1f1ab" xlink:to="loc_plrx_IncentiveStockOptionsAndNonqualifiedStockOptionsMember_019e65e1-522a-7bff-bdf9-29186d80a37d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_019e65e1-522a-7b98-9c87-cfb90354b61d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-76ed-aa60-2941ff223ce3" xlink:to="loc_us-gaap_PlanNameAxis_019e65e1-522a-7b98-9c87-cfb90354b61d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e65e1-522a-7b98-9c87-cfb90354b61d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_019e65e1-522a-7b98-9c87-cfb90354b61d" xlink:to="loc_us-gaap_PlanNameDomain_019e65e1-522a-7b98-9c87-cfb90354b61d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_019e65e1-522a-7535-b69a-b17b8f037626" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_019e65e1-522a-7b98-9c87-cfb90354b61d" xlink:to="loc_us-gaap_PlanNameDomain_019e65e1-522a-7535-b69a-b17b8f037626" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_TwoThousandFifteenAndTwoThousandTwentyEquityIncentivePlanMember_019e65e1-522a-7049-b131-d7fcbd2232a2" xlink:href="plrx-20260630.xsd#plrx_TwoThousandFifteenAndTwoThousandTwentyEquityIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_019e65e1-522a-7535-b69a-b17b8f037626" xlink:to="loc_plrx_TwoThousandFifteenAndTwoThousandTwentyEquityIncentivePlanMember_019e65e1-522a-7049-b131-d7fcbd2232a2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_019e65e1-522a-7d02-83ef-e37ed9c4dc0e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-71d9-bec4-ad691bb71e84" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_019e65e1-522a-7d02-83ef-e37ed9c4dc0e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_019e65e1-522a-7ba3-bbb9-44792d60d202" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_019e65e1-522a-7d02-83ef-e37ed9c4dc0e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_019e65e1-522a-7ba3-bbb9-44792d60d202" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_019e65e1-522a-7002-ad1b-765e726b350d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_019e65e1-522a-7d02-83ef-e37ed9c4dc0e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_019e65e1-522a-7002-ad1b-765e726b350d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_019e65e1-522a-787f-8f25-92d69d1b1620" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_019e65e1-522a-7d02-83ef-e37ed9c4dc0e" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_019e65e1-522a-787f-8f25-92d69d1b1620" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod_019e65e1-522a-7a4e-8846-4e89d14279e5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_019e65e1-522a-7d02-83ef-e37ed9c4dc0e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod_019e65e1-522a-7a4e-8846-4e89d14279e5" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_019e65e1-522a-7382-b65a-1f6dbf53daee" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_019e65e1-522a-7dfd-8f6b-e2384450b75c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-71d9-bec4-ad691bb71e84" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_019e65e1-522a-7dfd-8f6b-e2384450b75c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber_019e65e1-522a-7b0e-930a-1934aaeb316a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-71d9-bec4-ad691bb71e84" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber_019e65e1-522a-7b0e-930a-1934aaeb316a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_019e65e1-522a-7735-8d7f-73719b81420a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-71d9-bec4-ad691bb71e84" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_019e65e1-522a-7735-8d7f-73719b81420a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_019e65e1-522a-775c-911d-f71cde4ad7b8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_019e65e1-522a-7735-8d7f-73719b81420a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_019e65e1-522a-775c-911d-f71cde4ad7b8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_019e65e1-522a-713f-9883-e9de396e0de2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_019e65e1-522a-7735-8d7f-73719b81420a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_019e65e1-522a-713f-9883-e9de396e0de2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_019e65e1-522a-7a99-8718-eb71bf1de753" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_019e65e1-522a-7735-8d7f-73719b81420a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_019e65e1-522a-7a99-8718-eb71bf1de753" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice_019e65e1-522a-70fb-8a2d-28b9db01c0da" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_019e65e1-522a-7735-8d7f-73719b81420a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice_019e65e1-522a-70fb-8a2d-28b9db01c0da" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_019e65e1-522a-7084-a402-9bbca5ee99be" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_019e65e1-522a-7d7d-996f-0e2456a4d310" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-71d9-bec4-ad691bb71e84" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_019e65e1-522a-7d7d-996f-0e2456a4d310" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice_019e65e1-522a-7003-859a-b9164fbd946c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-71d9-bec4-ad691bb71e84" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice_019e65e1-522a-7003-859a-b9164fbd946c" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_019e65e1-522a-71af-bc31-6ba7b801712a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-71d9-bec4-ad691bb71e84" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_019e65e1-522a-71af-bc31-6ba7b801712a" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2_019e65e1-522a-7578-b93e-2d931be6b446" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_019e65e1-522a-71af-bc31-6ba7b801712a" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2_019e65e1-522a-7578-b93e-2d931be6b446" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_019e65e1-522a-7d9e-941e-47930b0a5e3d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_019e65e1-522a-71af-bc31-6ba7b801712a" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1_019e65e1-522a-7d9e-941e-47930b0a5e3d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1_019e65e1-522a-7e24-92cb-53d456191651" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_019e65e1-522a-71af-bc31-6ba7b801712a" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageRemainingContractualTerm1_019e65e1-522a-7e24-92cb-53d456191651" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_019e65e1-522a-76f0-adaf-201476fd21d4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_019e65e1-522a-71af-bc31-6ba7b801712a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingIntrinsicValue_019e65e1-522a-76f0-adaf-201476fd21d4" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1_019e65e1-522a-7a9a-9a80-10f8b4ae1bf8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_019e65e1-522a-71af-bc31-6ba7b801712a" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableIntrinsicValue1_019e65e1-522a-7a9a-9a80-10f8b4ae1bf8" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue_019e65e1-522a-74bc-bcaa-6759db25ee10" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsAdditionalDisclosuresAbstract_019e65e1-522a-71af-bc31-6ba7b801712a" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingAggregateIntrinsicValue_019e65e1-522a-74bc-bcaa-6759db25ee10" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationRestrictedStockUnitsNarrativeDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#EquityIncentivePlansandStockBasedCompensationRestrictedStockUnitsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationRestrictedStockUnitsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-732d-95b3-e6a954547357" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7d2b-8eaa-a56360e3e115" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-732d-95b3-e6a954547357" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7d2b-8eaa-a56360e3e115" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_019e65e1-522a-76d3-89c1-ab9fb0697a00" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7d2b-8eaa-a56360e3e115" xlink:to="loc_srt_RangeAxis_019e65e1-522a-76d3-89c1-ab9fb0697a00" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019e65e1-522a-76d3-89c1-ab9fb0697a00_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_019e65e1-522a-76d3-89c1-ab9fb0697a00" xlink:to="loc_srt_RangeMember_019e65e1-522a-76d3-89c1-ab9fb0697a00_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_019e65e1-522a-7e57-81d4-007ac15b253f" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_019e65e1-522a-76d3-89c1-ab9fb0697a00" xlink:to="loc_srt_RangeMember_019e65e1-522a-7e57-81d4-007ac15b253f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_019e65e1-522a-7c5e-a1fb-3996f16ebd3f" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_019e65e1-522a-7e57-81d4-007ac15b253f" xlink:to="loc_srt_MaximumMember_019e65e1-522a-7c5e-a1fb-3996f16ebd3f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7ba1-a9a9-a1e16980c7c0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7d2b-8eaa-a56360e3e115" xlink:to="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7ba1-a9a9-a1e16980c7c0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7ba1-a9a9-a1e16980c7c0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7ba1-a9a9-a1e16980c7c0" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7ba1-a9a9-a1e16980c7c0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7899-9000-454ff3143183" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7ba1-a9a9-a1e16980c7c0" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7899-9000-454ff3143183" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019e65e1-522a-73ea-a360-ee2918677c1a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7899-9000-454ff3143183" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019e65e1-522a-73ea-a360-ee2918677c1a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_019e65e1-522a-7332-ae15-01c4d6755aef" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-732d-95b3-e6a954547357" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardVestingPeriod1_019e65e1-522a-7332-ae15-01c4d6755aef" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_019e65e1-522a-7569-9f49-b85dfec9b6dd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-732d-95b3-e6a954547357" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedShareBasedAwardsOtherThanOptions_019e65e1-522a-7569-9f49-b85dfec9b6dd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019e65e1-522a-79e0-93f9-7c0e5f454b4b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-732d-95b3-e6a954547357" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationNonvestedAwardsTotalCompensationCostNotYetRecognizedPeriodForRecognition1_019e65e1-522a-79e0-93f9-7c0e5f454b4b" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationScheduleofRestrictedStockActivityDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#EquityIncentivePlansandStockBasedCompensationScheduleofRestrictedStockActivityDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationScheduleofRestrictedStockActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7dec-9a30-8efdb3ee2192" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-78cc-ac00-5b2e336f9202" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7dec-9a30-8efdb3ee2192" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-78cc-ac00-5b2e336f9202" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7dd9-b1ed-99db3f6fe219" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-78cc-ac00-5b2e336f9202" xlink:to="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7dd9-b1ed-99db3f6fe219" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7dd9-b1ed-99db3f6fe219_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7dd9-b1ed-99db3f6fe219" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7dd9-b1ed-99db3f6fe219_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7d52-8f45-20a457e48cbd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7dd9-b1ed-99db3f6fe219" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7d52-8f45-20a457e48cbd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019e65e1-522a-75de-aa4c-32b9b7d2bdb0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7d52-8f45-20a457e48cbd" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019e65e1-522a-75de-aa4c-32b9b7d2bdb0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019e65e1-522a-7764-ba5b-226b95228c01" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7dec-9a30-8efdb3ee2192" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019e65e1-522a-7764-ba5b-226b95228c01" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019e65e1-522a-7d81-bfb3-106ef18c3cbd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019e65e1-522a-7764-ba5b-226b95228c01" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019e65e1-522a-7d81-bfb3-106ef18c3cbd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_019e65e1-522a-7dad-bcde-2685cd0acd9b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019e65e1-522a-7764-ba5b-226b95228c01" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_019e65e1-522a-7dad-bcde-2685cd0acd9b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsReleasesInPeriod_019e65e1-522a-7496-876f-0b0685c64399" xlink:href="plrx-20260630.xsd#plrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsReleasesInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019e65e1-522a-7764-ba5b-226b95228c01" xlink:to="loc_plrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsReleasesInPeriod_019e65e1-522a-7496-876f-0b0685c64399" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_019e65e1-522a-78bd-ad54-ecc8acf5f748" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_019e65e1-522a-7764-ba5b-226b95228c01" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_019e65e1-522a-78bd-ad54-ecc8acf5f748" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_019e65e1-522a-7ed7-9b13-5031403fa842" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019e65e1-522a-76de-b092-c931da9c9046" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7dec-9a30-8efdb3ee2192" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019e65e1-522a-76de-b092-c931da9c9046" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_019e65e1-522a-7a5a-b3f7-b6ad186870d2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019e65e1-522a-76de-b092-c931da9c9046" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_019e65e1-522a-7a5a-b3f7-b6ad186870d2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019e65e1-522a-716f-a1da-8c7b2da6c866" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019e65e1-522a-76de-b092-c931da9c9046" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_019e65e1-522a-716f-a1da-8c7b2da6c866" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsReleasedWeightedAverageGrantDateFairValue_019e65e1-522a-7e39-a82c-24b7ae4f649b" xlink:href="plrx-20260630.xsd#plrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsReleasedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019e65e1-522a-76de-b092-c931da9c9046" xlink:to="loc_plrx_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsReleasedWeightedAverageGrantDateFairValue_019e65e1-522a-7e39-a82c-24b7ae4f649b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_019e65e1-522a-7ee6-a482-a9a1db578fc3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_019e65e1-522a-76de-b092-c931da9c9046" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_019e65e1-522a-7ee6-a482-a9a1db578fc3" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_019e65e1-522a-76f4-9b0d-af284251120d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensation2020EmployeeStockPurchasePlanNarrativeDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#EquityIncentivePlansandStockBasedCompensation2020EmployeeStockPurchasePlanNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensation2020EmployeeStockPurchasePlanNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-796a-905b-4c33f761406f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7841-841a-9a858015c265" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-796a-905b-4c33f761406f" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7841-841a-9a858015c265" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7cf0-a527-ea35ecc518e4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-7841-841a-9a858015c265" xlink:to="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7cf0-a527-ea35ecc518e4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7cf0-a527-ea35ecc518e4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7cf0-a527-ea35ecc518e4" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7cf0-a527-ea35ecc518e4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7c3a-9317-c1e8d8279e79" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-7cf0-a527-ea35ecc518e4" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7c3a-9317-c1e8d8279e79" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_TwoThousandAndTwentyEmployeeStockPurchasePlanMember_019e65e1-522a-72d9-b182-d7fc85f40cd7" xlink:href="plrx-20260630.xsd#plrx_TwoThousandAndTwentyEmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7c3a-9317-c1e8d8279e79" xlink:to="loc_plrx_TwoThousandAndTwentyEmployeeStockPurchasePlanMember_019e65e1-522a-72d9-b182-d7fc85f40cd7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfOutstandingStockMaximum_019e65e1-522a-7e36-8b06-00905f99e6ef" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfOutstandingStockMaximum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-796a-905b-4c33f761406f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardPercentageOfOutstandingStockMaximum_019e65e1-522a-7e36-8b06-00905f99e6ef" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_019e65e1-522a-7493-90f0-163f97e39711" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockCapitalSharesReservedForFutureIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-796a-905b-4c33f761406f" xlink:to="loc_us-gaap_CommonStockCapitalSharesReservedForFutureIssuance_019e65e1-522a-7493-90f0-163f97e39711" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_019e65e1-522a-7b36-91be-2a7932505f5a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-796a-905b-4c33f761406f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardMaximumEmployeeSubscriptionRate_019e65e1-522a-7b36-91be-2a7932505f5a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_EmployeeStockPurchasePlanOfferingPeriod_019e65e1-522a-7bf2-a082-e5d9cdcdcdb6" xlink:href="plrx-20260630.xsd#plrx_EmployeeStockPurchasePlanOfferingPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-796a-905b-4c33f761406f" xlink:to="loc_plrx_EmployeeStockPurchasePlanOfferingPeriod_019e65e1-522a-7bf2-a082-e5d9cdcdcdb6" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_CommonStockFairMarketValuePercentage_019e65e1-522a-708a-8e29-080a342a9cab" xlink:href="plrx-20260630.xsd#plrx_CommonStockFairMarketValuePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-796a-905b-4c33f761406f" xlink:to="loc_plrx_CommonStockFairMarketValuePercentage_019e65e1-522a-708a-8e29-080a342a9cab" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_019e65e1-522a-7bee-861b-6446364b34a1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-796a-905b-4c33f761406f" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_019e65e1-522a-7bee-861b-6446364b34a1" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_019e65e1-522a-7013-b559-d2faf6f29ee9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-796a-905b-4c33f761406f" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardSharesIssuedInPeriod_019e65e1-522a-7013-b559-d2faf6f29ee9" xlink:type="arc" order="6"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensation2020EmployeeStockPurchasePlanScheduleofBlackScholesOptionPricingModeltoEstimateStockbasedCompensationExpensefor2020EmployeeStockPurchasePlanDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#EquityIncentivePlansandStockBasedCompensation2020EmployeeStockPurchasePlanScheduleofBlackScholesOptionPricingModeltoEstimateStockbasedCompensationExpensefor2020EmployeeStockPurchasePlanDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensation2020EmployeeStockPurchasePlanScheduleofBlackScholesOptionPricingModeltoEstimateStockbasedCompensationExpensefor2020EmployeeStockPurchasePlanDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7eb4-bf1b-5064fc710b8c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-74ba-882a-d90ac2163ffe" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7eb4-bf1b-5064fc710b8c" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-74ba-882a-d90ac2163ffe" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019e65e1-522a-745e-95c9-1db5a42b85cb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-74ba-882a-d90ac2163ffe" xlink:to="loc_us-gaap_AwardTypeAxis_019e65e1-522a-745e-95c9-1db5a42b85cb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-745e-95c9-1db5a42b85cb_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-745e-95c9-1db5a42b85cb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-745e-95c9-1db5a42b85cb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7886-986b-8f360952ab46" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-745e-95c9-1db5a42b85cb" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7886-986b-8f360952ab46" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_TwoThousandAndTwentyEmployeeStockPurchasePlanMember_019e65e1-522a-7d6f-848e-16e696a87ee7" xlink:href="plrx-20260630.xsd#plrx_TwoThousandAndTwentyEmployeeStockPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7886-986b-8f360952ab46" xlink:to="loc_plrx_TwoThousandAndTwentyEmployeeStockPurchasePlanMember_019e65e1-522a-7d6f-848e-16e696a87ee7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_019e65e1-522a-7ce4-9e27-a5598fcb45e9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7eb4-bf1b-5064fc710b8c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate_019e65e1-522a-7ce4-9e27-a5598fcb45e9" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_019e65e1-522a-717d-aeec-564adf9af1a7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7eb4-bf1b-5064fc710b8c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate_019e65e1-522a-717d-aeec-564adf9af1a7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_019e65e1-522a-7a55-9d69-ad2e92b041db" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7eb4-bf1b-5064fc710b8c" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate_019e65e1-522a-7a55-9d69-ad2e92b041db" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_019e65e1-522a-7058-9e06-631147fccac6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7eb4-bf1b-5064fc710b8c" xlink:to="loc_us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1_019e65e1-522a-7058-9e06-631147fccac6" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationScheduleofStockbasedCompensationExpenseDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#EquityIncentivePlansandStockBasedCompensationScheduleofStockbasedCompensationExpenseDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationScheduleofStockbasedCompensationExpenseDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7789-afac-4d39766fa549" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-796f-817d-a791b57596ef" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7789-afac-4d39766fa549" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-796f-817d-a791b57596ef" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019e65e1-522a-704b-80f1-f3c21a0469a1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-796f-817d-a791b57596ef" xlink:to="loc_us-gaap_AwardTypeAxis_019e65e1-522a-704b-80f1-f3c21a0469a1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-704b-80f1-f3c21a0469a1_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-704b-80f1-f3c21a0469a1" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-704b-80f1-f3c21a0469a1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7456-9bc2-c0d9189bf1ef" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-704b-80f1-f3c21a0469a1" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7456-9bc2-c0d9189bf1ef" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_EmployeeStockOptionAndPurchasePlanMember_019e65e1-522a-71bc-8835-87eacb115924" xlink:href="plrx-20260630.xsd#plrx_EmployeeStockOptionAndPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7456-9bc2-c0d9189bf1ef" xlink:to="loc_plrx_EmployeeStockOptionAndPurchasePlanMember_019e65e1-522a-71bc-8835-87eacb115924" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019e65e1-522a-70a2-9f3d-793ee2dafcfd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7456-9bc2-c0d9189bf1ef" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019e65e1-522a-70a2-9f3d-793ee2dafcfd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_019e65e1-522a-7834-8f3d-fda9ca3ca282" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementOfIncomeLocationBalanceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-796f-817d-a791b57596ef" xlink:to="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_019e65e1-522a-7834-8f3d-fda9ca3ca282" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_019e65e1-522a-768a-b7a0-01c69b3a72c1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7789-afac-4d39766fa549" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_019e65e1-522a-768a-b7a0-01c69b3a72c1" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationScheduleofStockbasedCompensationExpenseDetails_1" xlink:type="simple" xlink:href="plrx-20260630.xsd#EquityIncentivePlansandStockBasedCompensationScheduleofStockbasedCompensationExpenseDetails_1"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/EquityIncentivePlansandStockBasedCompensationScheduleofStockbasedCompensationExpenseDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7789-afac-4d39766fa549" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-796f-817d-a791b57596ef" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7789-afac-4d39766fa549" xlink:to="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-796f-817d-a791b57596ef" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_019e65e1-522a-704b-80f1-f3c21a0469a1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable_019e65e1-522a-796f-817d-a791b57596ef" xlink:to="loc_us-gaap_AwardTypeAxis_019e65e1-522a-704b-80f1-f3c21a0469a1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-704b-80f1-f3c21a0469a1_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-704b-80f1-f3c21a0469a1" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-704b-80f1-f3c21a0469a1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7456-9bc2-c0d9189bf1ef" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_019e65e1-522a-704b-80f1-f3c21a0469a1" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7456-9bc2-c0d9189bf1ef" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_EmployeeStockOptionAndPurchasePlanMember_019e65e1-522a-71bc-8835-87eacb115924" xlink:href="plrx-20260630.xsd#plrx_EmployeeStockOptionAndPurchasePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7456-9bc2-c0d9189bf1ef" xlink:to="loc_plrx_EmployeeStockOptionAndPurchasePlanMember_019e65e1-522a-71bc-8835-87eacb115924" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019e65e1-522a-70a2-9f3d-793ee2dafcfd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_019e65e1-522a-7456-9bc2-c0d9189bf1ef" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019e65e1-522a-70a2-9f3d-793ee2dafcfd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_019e65e1-522a-768a-b7a0-01c69b3a72c1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems_019e65e1-522a-7789-afac-4d39766fa549" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_019e65e1-522a-768a-b7a0-01c69b3a72c1" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/SegmentsScheduleofSegmentReportingExpensesDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#SegmentsScheduleofSegmentReportingExpensesDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/SegmentsScheduleofSegmentReportingExpensesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingInformationLineItems_019e65e1-522a-7eb7-8bcd-eb11580f7833" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SegmentReportingInformationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_019e65e1-522a-7e1e-8abb-7a2fc47b05da" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019e65e1-522a-7eb7-8bcd-eb11580f7833" xlink:to="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_019e65e1-522a-7e1e-8abb-7a2fc47b05da" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_019e65e1-522a-776b-a878-ed8b0e3436ac" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfSegmentReportingInformationBySegmentTable_019e65e1-522a-7e1e-8abb-7a2fc47b05da" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_019e65e1-522a-776b-a878-ed8b0e3436ac" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_019e65e1-522a-776b-a878-ed8b0e3436ac_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_019e65e1-522a-776b-a878-ed8b0e3436ac" xlink:to="loc_us-gaap_SegmentDomain_019e65e1-522a-776b-a878-ed8b0e3436ac_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_019e65e1-522a-78f8-8141-39a069c01de9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_019e65e1-522a-776b-a878-ed8b0e3436ac" xlink:to="loc_us-gaap_SegmentDomain_019e65e1-522a-78f8-8141-39a069c01de9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_ReportableSegmentMember_019e65e1-522a-7a37-bf3d-8e1b45511248" xlink:href="plrx-20260630.xsd#plrx_ReportableSegmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_019e65e1-522a-78f8-8141-39a069c01de9" xlink:to="loc_plrx_ReportableSegmentMember_019e65e1-522a-7a37-bf3d-8e1b45511248" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingExpensesAbstract_019e65e1-522a-7469-b7c2-059f298836f7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingExpensesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019e65e1-522a-7eb7-8bcd-eb11580f7833" xlink:to="loc_us-gaap_OperatingExpensesAbstract_019e65e1-522a-7469-b7c2-059f298836f7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_ProgramExpenseIncludingClinicalTrialAndThirdPartyContractingCosts_019e65e1-522a-763a-a31d-9cb0f9228fb1" xlink:href="plrx-20260630.xsd#plrx_ProgramExpenseIncludingClinicalTrialAndThirdPartyContractingCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_019e65e1-522a-7469-b7c2-059f298836f7" xlink:to="loc_plrx_ProgramExpenseIncludingClinicalTrialAndThirdPartyContractingCosts_019e65e1-522a-763a-a31d-9cb0f9228fb1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_ClinicalTrialAndThirdPartyContractingCosts_019e65e1-522a-73d2-8cf6-c0965828cc17" xlink:href="plrx-20260630.xsd#plrx_ClinicalTrialAndThirdPartyContractingCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_019e65e1-522a-7469-b7c2-059f298836f7" xlink:to="loc_plrx_ClinicalTrialAndThirdPartyContractingCosts_019e65e1-522a-73d2-8cf6-c0965828cc17" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_ResearchAndDevelopmentExpenseAdjusted_019e65e1-522a-773b-ba62-ee522e739989" xlink:href="plrx-20260630.xsd#plrx_ResearchAndDevelopmentExpenseAdjusted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_019e65e1-522a-7469-b7c2-059f298836f7" xlink:to="loc_plrx_ResearchAndDevelopmentExpenseAdjusted_019e65e1-522a-773b-ba62-ee522e739989" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_GeneralAndAdministrativeExpenseAdjusted_019e65e1-522a-7fae-a772-d464cb687610" xlink:href="plrx-20260630.xsd#plrx_GeneralAndAdministrativeExpenseAdjusted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_019e65e1-522a-7469-b7c2-059f298836f7" xlink:to="loc_plrx_GeneralAndAdministrativeExpenseAdjusted_019e65e1-522a-7fae-a772-d464cb687610" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingOtherItemAmount_019e65e1-522a-7d99-9339-6c354c185178" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SegmentReportingOtherItemAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_019e65e1-522a-7469-b7c2-059f298836f7" xlink:to="loc_us-gaap_SegmentReportingOtherItemAmount_019e65e1-522a-7d99-9339-6c354c185178" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_019e65e1-522a-751a-ac86-712b3f31f60c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingExpensesAbstract_019e65e1-522a-7469-b7c2-059f298836f7" xlink:to="loc_us-gaap_OperatingIncomeLoss_019e65e1-522a-751a-ac86-712b3f31f60c" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReconciliationOfOperatingProfitLossFromSegmentsToConsolidatedAbstract_019e65e1-522a-7d63-8afb-36fdfb79d2ea" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ReconciliationOfOperatingProfitLossFromSegmentsToConsolidatedAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingInformationLineItems_019e65e1-522a-7eb7-8bcd-eb11580f7833" xlink:to="loc_us-gaap_ReconciliationOfOperatingProfitLossFromSegmentsToConsolidatedAbstract_019e65e1-522a-7d63-8afb-36fdfb79d2ea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_InterestAndOtherIncomeExpenseNet_019e65e1-522a-7530-91b9-60e7c5cc5ece" xlink:href="plrx-20260630.xsd#plrx_InterestAndOtherIncomeExpenseNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReconciliationOfOperatingProfitLossFromSegmentsToConsolidatedAbstract_019e65e1-522a-7d63-8afb-36fdfb79d2ea" xlink:to="loc_plrx_InterestAndOtherIncomeExpenseNet_019e65e1-522a-7530-91b9-60e7c5cc5ece" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_019e65e1-522a-7cb0-93c2-429e1203e12e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReconciliationOfOperatingProfitLossFromSegmentsToConsolidatedAbstract_019e65e1-522a-7d63-8afb-36fdfb79d2ea" xlink:to="loc_us-gaap_InterestExpenseNonoperating_019e65e1-522a-7cb0-93c2-429e1203e12e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_019e65e1-522a-71f1-9b09-4207fd1b16fc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReconciliationOfOperatingProfitLossFromSegmentsToConsolidatedAbstract_019e65e1-522a-7d63-8afb-36fdfb79d2ea" xlink:to="loc_us-gaap_NetIncomeLoss_019e65e1-522a-71f1-9b09-4207fd1b16fc" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/LeasesNarrativeDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#LeasesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/LeasesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e65e1-522a-73d9-9808-e65f514824ff" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeLeaseDescriptionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeLeaseDescriptionTable_019e65e1-522a-7394-a3a1-7e7556ab23ba" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeLeaseDescriptionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e65e1-522a-73d9-9808-e65f514824ff" xlink:to="loc_us-gaap_LesseeLeaseDescriptionTable_019e65e1-522a-7394-a3a1-7e7556ab23ba" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementGeographicalAxis_019e65e1-522a-75f3-a1a4-e8c57f376cdd" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_StatementGeographicalAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_019e65e1-522a-7394-a3a1-7e7556ab23ba" xlink:to="loc_srt_StatementGeographicalAxis_019e65e1-522a-75f3-a1a4-e8c57f376cdd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019e65e1-522a-75f3-a1a4-e8c57f376cdd_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementGeographicalAxis_019e65e1-522a-75f3-a1a4-e8c57f376cdd" xlink:to="loc_srt_SegmentGeographicalDomain_019e65e1-522a-75f3-a1a4-e8c57f376cdd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_SegmentGeographicalDomain_019e65e1-522a-7526-bb38-ae0fa9b3bca4" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_SegmentGeographicalDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementGeographicalAxis_019e65e1-522a-75f3-a1a4-e8c57f376cdd" xlink:to="loc_srt_SegmentGeographicalDomain_019e65e1-522a-7526-bb38-ae0fa9b3bca4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_stpr_CA_019e65e1-522a-7478-8e46-97ceee01f96a" xlink:href="https://xbrl.sec.gov/stpr/2026/stpr-2026.xsd#stpr_CA"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_SegmentGeographicalDomain_019e65e1-522a-7526-bb38-ae0fa9b3bca4" xlink:to="loc_stpr_CA_019e65e1-522a-7478-8e46-97ceee01f96a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_019e65e1-522a-7b19-81cd-c077e4b739a2" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_019e65e1-522a-7394-a3a1-7e7556ab23ba" xlink:to="loc_srt_CounterpartyNameAxis_019e65e1-522a-7b19-81cd-c077e4b739a2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019e65e1-522a-7b19-81cd-c077e4b739a2_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_019e65e1-522a-7b19-81cd-c077e4b739a2" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019e65e1-522a-7b19-81cd-c077e4b739a2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019e65e1-522a-72aa-bcb7-ae94d5bff5d9" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_019e65e1-522a-7b19-81cd-c077e4b739a2" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019e65e1-522a-72aa-bcb7-ae94d5bff5d9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_LandlordMember_019e65e1-522a-7987-9096-1877dcd69204" xlink:href="plrx-20260630.xsd#plrx_LandlordMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_019e65e1-522a-72aa-bcb7-ae94d5bff5d9" xlink:to="loc_plrx_LandlordMember_019e65e1-522a-7987-9096-1877dcd69204" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_019e65e1-522a-7ce6-b6a8-c7c753f53dea" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_019e65e1-522a-7394-a3a1-7e7556ab23ba" xlink:to="loc_us-gaap_CreditFacilityAxis_019e65e1-522a-7ce6-b6a8-c7c753f53dea" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_019e65e1-522a-7ce6-b6a8-c7c753f53dea_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CreditFacilityAxis_019e65e1-522a-7ce6-b6a8-c7c753f53dea" xlink:to="loc_us-gaap_CreditFacilityDomain_019e65e1-522a-7ce6-b6a8-c7c753f53dea_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_019e65e1-522a-71d7-bfda-ebbf52443116" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CreditFacilityAxis_019e65e1-522a-7ce6-b6a8-c7c753f53dea" xlink:to="loc_us-gaap_CreditFacilityDomain_019e65e1-522a-71d7-bfda-ebbf52443116" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LetterOfCreditMember_019e65e1-522a-7dc9-b09a-9a40a3adcb7a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LetterOfCreditMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_019e65e1-522a-71d7-bfda-ebbf52443116" xlink:to="loc_us-gaap_LetterOfCreditMember_019e65e1-522a-7dc9-b09a-9a40a3adcb7a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityAxis_019e65e1-522a-7cdd-aef8-a1e39f56291d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LineOfCreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LesseeLeaseDescriptionTable_019e65e1-522a-7394-a3a1-7e7556ab23ba" xlink:to="loc_us-gaap_LineOfCreditFacilityAxis_019e65e1-522a-7cdd-aef8-a1e39f56291d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLenderDomain_019e65e1-522a-7cdd-aef8-a1e39f56291d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LineOfCreditFacilityLenderDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LineOfCreditFacilityAxis_019e65e1-522a-7cdd-aef8-a1e39f56291d" xlink:to="loc_us-gaap_LineOfCreditFacilityLenderDomain_019e65e1-522a-7cdd-aef8-a1e39f56291d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLenderDomain_019e65e1-522a-7fa1-b914-73e0c259bb1e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LineOfCreditFacilityLenderDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LineOfCreditFacilityAxis_019e65e1-522a-7cdd-aef8-a1e39f56291d" xlink:to="loc_us-gaap_LineOfCreditFacilityLenderDomain_019e65e1-522a-7fa1-b914-73e0c259bb1e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_PliantTherapeuticsMember_019e65e1-522a-7037-bd15-ba532b55bc93" xlink:href="plrx-20260630.xsd#plrx_PliantTherapeuticsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLenderDomain_019e65e1-522a-7fa1-b914-73e0c259bb1e" xlink:to="loc_plrx_PliantTherapeuticsMember_019e65e1-522a-7037-bd15-ba532b55bc93" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_plrx_LeasedSpaceUnderNonCancellableOperatingLease_019e65e1-522a-7696-92ce-999365cc71fa" xlink:href="plrx-20260630.xsd#plrx_LeasedSpaceUnderNonCancellableOperatingLease"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e65e1-522a-73d9-9808-e65f514824ff" xlink:to="loc_plrx_LeasedSpaceUnderNonCancellableOperatingLease_019e65e1-522a-7696-92ce-999365cc71fa" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseTermOfContract_019e65e1-522a-7040-802a-4ecad3b9256f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseTermOfContract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e65e1-522a-73d9-9808-e65f514824ff" xlink:to="loc_us-gaap_LesseeOperatingLeaseTermOfContract_019e65e1-522a-7040-802a-4ecad3b9256f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_019e65e1-522a-7996-a59c-e5854c48b6de" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseRenewalTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e65e1-522a-73d9-9808-e65f514824ff" xlink:to="loc_us-gaap_LesseeOperatingLeaseRenewalTerm_019e65e1-522a-7996-a59c-e5854c48b6de" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019e65e1-522a-7cde-9460-ca86c9796828" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e65e1-522a-73d9-9808-e65f514824ff" xlink:to="loc_us-gaap_LesseeOperatingLeaseLiabilityPaymentsDue_019e65e1-522a-7cde-9460-ca86c9796828" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCredit_019e65e1-522a-7ed4-a0ea-bb6083b1dee6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LineOfCredit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e65e1-522a-73d9-9808-e65f514824ff" xlink:to="loc_us-gaap_LineOfCredit_019e65e1-522a-7ed4-a0ea-bb6083b1dee6" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_019e65e1-522a-7dbd-a8e6-7dbf5440baf3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LesseeLeaseDescriptionLineItems_019e65e1-522a-73d9-9808-e65f514824ff" xlink:to="loc_us-gaap_RightOfUseAssetObtainedInExchangeForOperatingLeaseLiability_019e65e1-522a-7dbd-a8e6-7dbf5440baf3" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.pliantrx.com/role/NetLossPerShareAttributabletoCommonStockholdersDetails" xlink:type="simple" xlink:href="plrx-20260630.xsd#NetLossPerShareAttributabletoCommonStockholdersDetails"/>
  <link:definitionLink xlink:role="http://www.pliantrx.com/role/NetLossPerShareAttributabletoCommonStockholdersDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_019e65e1-522a-7add-bd9a-b4a271f03058" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_019e65e1-522a-7954-be19-c521373292dc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_019e65e1-522a-7add-bd9a-b4a271f03058" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_019e65e1-522a-7954-be19-c521373292dc" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019e65e1-522a-7270-bb8d-14cf7ca25f5a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_019e65e1-522a-7954-be19-c521373292dc" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019e65e1-522a-7270-bb8d-14cf7ca25f5a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019e65e1-522a-7270-bb8d-14cf7ca25f5a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019e65e1-522a-7270-bb8d-14cf7ca25f5a" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019e65e1-522a-7270-bb8d-14cf7ca25f5a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019e65e1-522a-7c79-a3cb-fd402567457c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_019e65e1-522a-7270-bb8d-14cf7ca25f5a" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019e65e1-522a-7c79-a3cb-fd402567457c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_019e65e1-522a-7281-9a48-dfef8efbfbf5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019e65e1-522a-7c79-a3cb-fd402567457c" xlink:to="loc_us-gaap_EmployeeStockOptionMember_019e65e1-522a-7281-9a48-dfef8efbfbf5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockUnitsRSUMember_019e65e1-522a-7ed7-b53a-c02723f8c1ce" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedStockUnitsRSUMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_019e65e1-522a-7c79-a3cb-fd402567457c" xlink:to="loc_us-gaap_RestrictedStockUnitsRSUMember_019e65e1-522a-7ed7-b53a-c02723f8c1ce" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_019e65e1-522a-72a1-9486-3bb9f57ed455" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_019e65e1-522a-7add-bd9a-b4a271f03058" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_019e65e1-522a-72a1-9486-3bb9f57ed455" xlink:type="arc" order="0"/>
  </link:definitionLink>
</link:linkbase>
