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

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:019b7fad-57b3-77c6-8796-dc32455779aa,g:3feb90f9-15ee-4193-aa43-beb833de7d4c-->
<xs:schema xmlns:xs="http://www.w3.org/2001/XMLSchema" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:rytm="http://www.rhythmtx.com/20260331" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2024-01-31" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" attributeFormDefault="unqualified" elementFormDefault="qualified" targetNamespace="http://www.rhythmtx.com/20260331">
  <xs:import namespace="http://fasb.org/srt/2025" schemaLocation="https://xbrl.fasb.org/srt/2025/elts/srt-2025.xsd"/>
  <xs:import namespace="http://fasb.org/us-gaap/2025" schemaLocation="https://xbrl.fasb.org/us-gaap/2025/elts/us-gaap-2025.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/instance" schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/2003/linkbase" schemaLocation="http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd"/>
  <xs:import namespace="http://www.xbrl.org/dtr/type/2024-01-31" schemaLocation="https://www.xbrl.org/dtr/type/2024-01-31/types.xsd"/>
  <xs:import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/country/2025" schemaLocation="https://xbrl.sec.gov/country/2025/country-2025.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/dei/2025" schemaLocation="https://xbrl.sec.gov/dei/2025/dei-2025.xsd"/>
  <xs:import namespace="http://xbrl.sec.gov/ecd/2025" schemaLocation="https://xbrl.sec.gov/ecd/2025/ecd-2025.xsd"/>
  <xs:annotation>
    <xs:appinfo>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="rytm-20260331_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="rytm-20260331_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="rytm-20260331_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:type="simple"/>
      <link:linkbaseRef xmlns:xlink="http://www.w3.org/1999/xlink" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" xlink:href="rytm-20260331_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" xlink:type="simple"/>
      <link:roleType id="Cover" roleURI="http://www.rhythmtx.com/role/Cover">
        <link:definition>0000001 - Document - Cover</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedBalanceSheets" roleURI="http://www.rhythmtx.com/role/CondensedConsolidatedBalanceSheets">
        <link:definition>9952151 - Statement - Condensed Consolidated Balance Sheets</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedBalanceSheetsParenthetical" roleURI="http://www.rhythmtx.com/role/CondensedConsolidatedBalanceSheetsParenthetical">
        <link:definition>9952152 - Statement - Condensed Consolidated Balance Sheets (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedStatementsofOperationsandComprehensiveLoss" roleURI="http://www.rhythmtx.com/role/CondensedConsolidatedStatementsofOperationsandComprehensiveLoss">
        <link:definition>9952153 - Statement - Condensed Consolidated Statements of Operations and Comprehensive Loss</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedStatementsofOperationsandComprehensiveLoss_1" roleURI="http://www.rhythmtx.com/role/CondensedConsolidatedStatementsofOperationsandComprehensiveLoss_1">
        <link:definition>9952153 - Statement - Condensed Consolidated Statements of Operations and Comprehensive Loss</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedStatementsofConvertiblePreferredStockStockholdersEquity" roleURI="http://www.rhythmtx.com/role/CondensedConsolidatedStatementsofConvertiblePreferredStockStockholdersEquity">
        <link:definition>9952154 - Statement - Condensed Consolidated Statements of Convertible Preferred Stock &amp; Stockholders' Equity</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedStatementsofConvertiblePreferredStockStockholdersEquityParenthetical" roleURI="http://www.rhythmtx.com/role/CondensedConsolidatedStatementsofConvertiblePreferredStockStockholdersEquityParenthetical">
        <link:definition>9952155 - Statement - Condensed Consolidated Statements of Convertible Preferred Stock &amp; Stockholders' Equity (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CondensedConsolidatedStatementsofCashFlows" roleURI="http://www.rhythmtx.com/role/CondensedConsolidatedStatementsofCashFlows">
        <link:definition>9952156 - Statement - Condensed Consolidated Statements of Cash Flows</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NatureofBusiness" roleURI="http://www.rhythmtx.com/role/NatureofBusiness">
        <link:definition>9952157 - Disclosure - Nature of Business</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPolicies" roleURI="http://www.rhythmtx.com/role/SummaryofSignificantAccountingPolicies">
        <link:definition>9952158 - Disclosure - Summary of Significant Accounting Policies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AssetAcquisitions" roleURI="http://www.rhythmtx.com/role/AssetAcquisitions">
        <link:definition>9952159 - Disclosure - Asset Acquisitions</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="Inventory" roleURI="http://www.rhythmtx.com/role/Inventory">
        <link:definition>9952160 - Disclosure - Inventory</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AccruedExpensesandOtherCurrentLiabilities" roleURI="http://www.rhythmtx.com/role/AccruedExpensesandOtherCurrentLiabilities">
        <link:definition>9952161 - Disclosure - Accrued Expenses and Other Current Liabilities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueofFinancialAssetsandLiabilities" roleURI="http://www.rhythmtx.com/role/FairValueofFinancialAssetsandLiabilities">
        <link:definition>9952162 - Disclosure - Fair Value of Financial Assets and Liabilities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IntangibleAssetsNet" roleURI="http://www.rhythmtx.com/role/IntangibleAssetsNet">
        <link:definition>9952163 - Disclosure - Intangible Assets, Net</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxes" roleURI="http://www.rhythmtx.com/role/IncomeTaxes">
        <link:definition>9952164 - Disclosure - Income Taxes</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SeriesAConvertiblePreferredStock" roleURI="http://www.rhythmtx.com/role/SeriesAConvertiblePreferredStock">
        <link:definition>9952165 - Disclosure - Series A Convertible Preferred Stock</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStock" roleURI="http://www.rhythmtx.com/role/CommonStock">
        <link:definition>9952166 - Disclosure - Common Stock</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="RelatedPartyTransactions" roleURI="http://www.rhythmtx.com/role/RelatedPartyTransactions">
        <link:definition>9952167 - Disclosure - Related-Party Transactions</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SignificantAgreements" roleURI="http://www.rhythmtx.com/role/SignificantAgreements">
        <link:definition>9952168 - Disclosure - Significant Agreements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LongTermObligations" roleURI="http://www.rhythmtx.com/role/LongTermObligations">
        <link:definition>9952169 - Disclosure - Long-Term Obligations</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingencies" roleURI="http://www.rhythmtx.com/role/CommitmentsandContingencies">
        <link:definition>9952170 - Disclosure - Commitments and Contingencies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SegmentandGeographicInformation" roleURI="http://www.rhythmtx.com/role/SegmentandGeographicInformation">
        <link:definition>9952171 - Disclosure - Segment and Geographic Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SubsequentEvents" roleURI="http://www.rhythmtx.com/role/SubsequentEvents">
        <link:definition>9952172 - Disclosure - Subsequent Events</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesPolicies" roleURI="http://www.rhythmtx.com/role/SummaryofSignificantAccountingPoliciesPolicies">
        <link:definition>9955511 - Disclosure - Summary of Significant Accounting Policies (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesTables" roleURI="http://www.rhythmtx.com/role/SummaryofSignificantAccountingPoliciesTables">
        <link:definition>9955512 - Disclosure - Summary of Significant Accounting Policies (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="InventoryTables" roleURI="http://www.rhythmtx.com/role/InventoryTables">
        <link:definition>9955513 - Disclosure - Inventory (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AccruedExpensesandOtherCurrentLiabilitiesTables" roleURI="http://www.rhythmtx.com/role/AccruedExpensesandOtherCurrentLiabilitiesTables">
        <link:definition>9955514 - Disclosure - Accrued Expenses and Other Current Liabilities (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueofFinancialAssetsandLiabilitiesTables" roleURI="http://www.rhythmtx.com/role/FairValueofFinancialAssetsandLiabilitiesTables">
        <link:definition>9955515 - Disclosure - Fair Value of Financial Assets and Liabilities (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IntangibleAssetsNetTables" roleURI="http://www.rhythmtx.com/role/IntangibleAssetsNetTables">
        <link:definition>9955516 - Disclosure - Intangible Assets, Net (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SegmentandGeographicInformationTables" roleURI="http://www.rhythmtx.com/role/SegmentandGeographicInformationTables">
        <link:definition>9955517 - Disclosure - Segment and Geographic Information (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="NatureofBusinessDetails" roleURI="http://www.rhythmtx.com/role/NatureofBusinessDetails">
        <link:definition>9955518 - Disclosure - Nature of Business (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesSegmentandGeographicInformationDetails" roleURI="http://www.rhythmtx.com/role/SummaryofSignificantAccountingPoliciesSegmentandGeographicInformationDetails">
        <link:definition>9955519 - Disclosure - Summary of Significant Accounting Policies - Segment and Geographic Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesOffBalanceSheetRiskandConcentrationsofCreditRiskDetails" roleURI="http://www.rhythmtx.com/role/SummaryofSignificantAccountingPoliciesOffBalanceSheetRiskandConcentrationsofCreditRiskDetails">
        <link:definition>9955520 - Disclosure - Summary of Significant Accounting Policies - Off-Balance Sheet Risk and Concentrations of Credit Risk (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesRevenueRecognitionDetails" roleURI="http://www.rhythmtx.com/role/SummaryofSignificantAccountingPoliciesRevenueRecognitionDetails">
        <link:definition>9955521 - Disclosure - Summary of Significant Accounting Policies - Revenue Recognition (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesImpairmentofLongLivedAssetsDetails" roleURI="http://www.rhythmtx.com/role/SummaryofSignificantAccountingPoliciesImpairmentofLongLivedAssetsDetails">
        <link:definition>9955522 - Disclosure - Summary of Significant Accounting Policies - Impairment of Long-Lived Assets (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesForeignCurrencyTranslationDetails" roleURI="http://www.rhythmtx.com/role/SummaryofSignificantAccountingPoliciesForeignCurrencyTranslationDetails">
        <link:definition>9955523 - Disclosure - Summary of Significant Accounting Policies - Foreign Currency Translation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SummaryofSignificantAccountingPoliciesNetlosspershareDetails" roleURI="http://www.rhythmtx.com/role/SummaryofSignificantAccountingPoliciesNetlosspershareDetails">
        <link:definition>9955524 - Disclosure - Summary of Significant Accounting Policies - Net loss per share (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AssetAcquisitionsNarrativeDetails" roleURI="http://www.rhythmtx.com/role/AssetAcquisitionsNarrativeDetails">
        <link:definition>9955525 - Disclosure - Asset Acquisitions - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="InventoryDetails" roleURI="http://www.rhythmtx.com/role/InventoryDetails">
        <link:definition>9955526 - Disclosure - Inventory (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="AccruedExpensesandOtherCurrentLiabilitiesDetails" roleURI="http://www.rhythmtx.com/role/AccruedExpensesandOtherCurrentLiabilitiesDetails">
        <link:definition>9955527 - Disclosure - Accrued Expenses and Other Current Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueofFinancialAssetsandLiabilitiesNarrativeDetails" roleURI="http://www.rhythmtx.com/role/FairValueofFinancialAssetsandLiabilitiesNarrativeDetails">
        <link:definition>9955528 - Disclosure - Fair Value of Financial Assets and Liabilities - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueofFinancialAssetsandLiabilitiesFinancialAssetsandLiabilitiesMeasuredatFairValueonaRecurringBasisDetails" roleURI="http://www.rhythmtx.com/role/FairValueofFinancialAssetsandLiabilitiesFinancialAssetsandLiabilitiesMeasuredatFairValueonaRecurringBasisDetails">
        <link:definition>9955529 - Disclosure - Fair Value of Financial Assets and Liabilities - Financial Assets and Liabilities Measured at Fair Value on a Recurring Basis (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueofFinancialAssetsandLiabilitiesChangesinEmbeddedDerivativeLiabilityDetails" roleURI="http://www.rhythmtx.com/role/FairValueofFinancialAssetsandLiabilitiesChangesinEmbeddedDerivativeLiabilityDetails">
        <link:definition>9955530 - Disclosure - Fair Value of Financial Assets and Liabilities - Changes in Embedded Derivative Liability (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="FairValueofFinancialAssetsandLiabilitiesMarketableSecuritiesDetails" roleURI="http://www.rhythmtx.com/role/FairValueofFinancialAssetsandLiabilitiesMarketableSecuritiesDetails">
        <link:definition>9955531 - Disclosure - Fair Value of Financial Assets and Liabilities - Marketable Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IntangibleAssetsScheduleoffinitelivedintangibleassetsDetails" roleURI="http://www.rhythmtx.com/role/IntangibleAssetsScheduleoffinitelivedintangibleassetsDetails">
        <link:definition>9955532 - Disclosure - Intangible Assets - Schedule of finite-lived intangible assets (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IntangibleAssetsNarrativeDetails" roleURI="http://www.rhythmtx.com/role/IntangibleAssetsNarrativeDetails">
        <link:definition>9955533 - Disclosure - Intangible Assets - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IntangibleAssetsNetAmortizationexpenseDetails" roleURI="http://www.rhythmtx.com/role/IntangibleAssetsNetAmortizationexpenseDetails">
        <link:definition>9955534 - Disclosure - Intangible Assets, Net - Amortization expense (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="IncomeTaxesDetails" roleURI="http://www.rhythmtx.com/role/IncomeTaxesDetails">
        <link:definition>9955535 - Disclosure - Income Taxes (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SeriesAConvertiblePreferredStockDetails" roleURI="http://www.rhythmtx.com/role/SeriesAConvertiblePreferredStockDetails">
        <link:definition>9955536 - Disclosure - Series A Convertible Preferred Stock (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommonStockDetails" roleURI="http://www.rhythmtx.com/role/CommonStockDetails">
        <link:definition>9955537 - Disclosure - Common Stock (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SignificantAgreementsDetails" roleURI="http://www.rhythmtx.com/role/SignificantAgreementsDetails">
        <link:definition>9955538 - Disclosure - Significant Agreements (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="LongTermObligationsDetails" roleURI="http://www.rhythmtx.com/role/LongTermObligationsDetails">
        <link:definition>9955539 - Disclosure - Long-Term Obligations (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="CommitmentsandContingenciesDetails" roleURI="http://www.rhythmtx.com/role/CommitmentsandContingenciesDetails">
        <link:definition>9955540 - Disclosure - Commitments and Contingencies (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SegmentandGeographicInformationNarrativeDetails" roleURI="http://www.rhythmtx.com/role/SegmentandGeographicInformationNarrativeDetails">
        <link:definition>9955541 - Disclosure - Segment and Geographic Information - Narrative (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SegmentandGeographicInformationProfitlossDetails" roleURI="http://www.rhythmtx.com/role/SegmentandGeographicInformationProfitlossDetails">
        <link:definition>9955542 - Disclosure - Segment and Geographic Information - Profit (loss) (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType id="SegmentandGeographicInformationRevenuesDetails" roleURI="http://www.rhythmtx.com/role/SegmentandGeographicInformationRevenuesDetails">
        <link:definition>9955543 - Disclosure - Segment and Geographic Information - Revenues (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
    </xs:appinfo>
  </xs:annotation>
  <xs:element id="rytm_SeriesAConvertiblePreferredStockMember" abstract="true" name="SeriesAConvertiblePreferredStockMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_ConvertiblePreferredStockDividends" abstract="false" name="ConvertiblePreferredStockDividends" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_TemporaryEquitySharesConversionOfConvertibleSecurities" abstract="false" name="TemporaryEquitySharesConversionOfConvertibleSecurities" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="rytm_TemporaryEquityValueConversionOfConvertibleSecurities" abstract="false" name="TemporaryEquityValueConversionOfConvertibleSecurities" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_StockIssuedDuringPeriodSharesStockOptionsAndRestrictedStockUnitsVesting" abstract="false" name="StockIssuedDuringPeriodSharesStockOptionsAndRestrictedStockUnitsVesting" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="rytm_StockIssuedDuringPeriodValueStockOptionsAndRestrictedStockUnitsVesting" abstract="false" name="StockIssuedDuringPeriodValueStockOptionsAndRestrictedStockUnitsVesting" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_Depreciationdepletionandamortizationpropertyandequipmentincludingintangibleassets" abstract="false" name="Depreciationdepletionandamortizationpropertyandequipmentincludingintangibleassets" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_NonCashInterestExpense" abstract="false" name="NonCashInterestExpense" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_NonCashAccretionAndAmortizationOfShortTermInvestments" abstract="false" name="NonCashAccretionAndAmortizationOfShortTermInvestments" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_DeferredRentExpense" abstract="false" name="DeferredRentExpense" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_TemporaryEquityTextBlock" abstract="false" name="TemporaryEquityTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="rytm_SignificantAgreementsAbstract" abstract="true" name="SignificantAgreementsAbstract" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:stringItemType"/>
  <xs:element id="rytm_LicenseAgreementsAccountingPolicyPolicyTextBlock" abstract="false" name="LicenseAgreementsAccountingPolicyPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="rytm_DeferredRoyaltyObligationAccountingPolicyPolicyTextBlock" abstract="false" name="DeferredRoyaltyObligationAccountingPolicyPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="rytm_CostOfProductSalesPolicyTextBlock" abstract="false" name="CostOfProductSalesPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="rytm_ImpairmentOrDisposalOfLongLivedAssetsAndPropertyPlantAndEquipmentPolicyTextBlock" abstract="false" name="ImpairmentOrDisposalOfLongLivedAssetsAndPropertyPlantAndEquipmentPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="rytm_AcquiredFiniteLivedIntangiblesPolicyTextBlock" abstract="false" name="AcquiredFiniteLivedIntangiblesPolicyTextBlock" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:textBlockItemType"/>
  <xs:element id="rytm_CustomerOneMember" abstract="true" name="CustomerOneMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_CustomerTwoMember" abstract="true" name="CustomerTwoMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_NumberOfFederallyInsuredFinancialInstitutions" abstract="false" name="NumberOfFederallyInsuredFinancialInstitutions" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="rytm_NumberOfPharmaciesProductSold" abstract="false" name="NumberOfPharmaciesProductSold" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="rytm_LGChemLtdMember" abstract="true" name="LGChemLtdMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_LicenseAgreementAndShareIssuanceAgreementMember" abstract="true" name="LicenseAgreementAndShareIssuanceAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_ThresholdPeriodForCalculatingWeightedAverageClosingPricePerShare" abstract="false" name="ThresholdPeriodForCalculatingWeightedAverageClosingPricePerShare" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="rytm_StockIssuedDuringPeriodValueNewIssuesLicenseAgreement" abstract="false" name="StockIssuedDuringPeriodValueNewIssuesLicenseAgreement" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_LicenseAgreementConsiderationPaymentReceivedInCash" abstract="false" name="LicenseAgreementConsiderationPaymentReceivedInCash" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_LockUpPeriodForSubsequentCashPayment" abstract="false" name="LockUpPeriodForSubsequentCashPayment" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="rytm_PaymentForAdditionalConsiderationOnAssetAcquisition" abstract="false" name="PaymentForAdditionalConsiderationOnAssetAcquisition" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_AggregatePaymentUponAchievementOfDevelopmentAndCommercialMilestones" abstract="false" name="AggregatePaymentUponAchievementOfDevelopmentAndCommercialMilestones" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_AccruedResearchAndDevelopmentCosts" abstract="false" name="AccruedResearchAndDevelopmentCosts" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_AccruedPayrollRelatedExpenseCurrent" abstract="false" name="AccruedPayrollRelatedExpenseCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_RoyaltiesCurrent" abstract="false" name="RoyaltiesCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_SalesAllowancesAccruedCurrent" abstract="false" name="SalesAllowancesAccruedCurrent" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_CorporateDebtSecuritiesAndCommercialPaperMember" abstract="true" name="CorporateDebtSecuritiesAndCommercialPaperMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityAssetValueBeginningBalance" abstract="false" name="FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityAssetValueBeginningBalance" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_CapitalizedMilestonesMember" abstract="true" name="CapitalizedMilestonesMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_FiniteLivedIntangibleAssetExpectedAmortizationAfterYearFour" abstract="false" name="FiniteLivedIntangibleAssetExpectedAmortizationAfterYearFour" nillable="true" xbrli:periodType="instant" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_ConvertiblePreferredStockHolderAxis" abstract="true" name="ConvertiblePreferredStockHolderAxis" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:dimensionItem" type="xbrli:stringItemType"/>
  <xs:element id="rytm_ConvertiblePreferredStockHolderDomain" abstract="true" name="ConvertiblePreferredStockHolderDomain" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_OneHolderOfSeriesConvertiblePreferredStockMember" abstract="true" name="OneHolderOfSeriesConvertiblePreferredStockMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_SecondHolderOfSeriesConvertiblePreferredStockMember" abstract="true" name="SecondHolderOfSeriesConvertiblePreferredStockMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_TemporaryEquityStockIssuedDuringPeriodSharesNewIssues" abstract="false" name="TemporaryEquityStockIssuedDuringPeriodSharesNewIssues" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="rytm_TemporaryEquityAggregatePurchasePrice" abstract="false" name="TemporaryEquityAggregatePurchasePrice" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_TemporaryEquityStockIssuanceCost" abstract="false" name="TemporaryEquityStockIssuanceCost" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_TemporaryEquitySharesIssuedPricePerShare" abstract="false" name="TemporaryEquitySharesIssuedPricePerShare" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:perShareItemType"/>
  <xs:element id="rytm_TemporaryEquityFairValueDisclosure" abstract="false" name="TemporaryEquityFairValueDisclosure" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_TemporaryEquityLiquidationPreferenceMultiplierFactor" abstract="false" name="TemporaryEquityLiquidationPreferenceMultiplierFactor" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:pureItemType"/>
  <xs:element id="rytm_TemporaryEquityDividendRatePercentage" abstract="false" name="TemporaryEquityDividendRatePercentage" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="rytm_PercentageOfOwnershipAfterConversion" abstract="false" name="PercentageOfOwnershipAfterConversion" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="rytm_LimitedVotingRightsShares" abstract="false" name="LimitedVotingRightsShares" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="rytm_StepUpInterestRatePercentage" abstract="false" name="StepUpInterestRatePercentage" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="rytm_PreferredStockSharesAuthorizedIncludingTemporaryEquity" abstract="false" name="PreferredStockSharesAuthorizedIncludingTemporaryEquity" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="rytm_StockOptionsRestrictedStockUnitsPerformanceStockUnitsInAggregateMember" abstract="true" name="StockOptionsRestrictedStockUnitsPerformanceStockUnitsInAggregateMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_TwoThousandSeventeenEmployeeAndEmploymentInducementPlan2022stockPurchasePlansInAggregateMember" abstract="true" name="TwoThousandSeventeenEmployeeAndEmploymentInducementPlan2022stockPurchasePlansInAggregateMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_StockIncentivePlan2017Member" abstract="true" name="StockIncentivePlan2017Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_TwoThousandSeventeenEmployeeStockPurchasePlanMember" abstract="true" name="TwoThousandSeventeenEmployeeStockPurchasePlanMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_EmploymentInducementPlan2022Member" abstract="true" name="EmploymentInducementPlan2022Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_FollowOnOfferingMember" abstract="true" name="FollowOnOfferingMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_AtMarketOfferingsMember" abstract="true" name="AtMarketOfferingsMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_NumberOfSharesToBeIssued" abstract="false" name="NumberOfSharesToBeIssued" nillable="true" xbrli:periodType="instant" substitutionGroup="xbrli:item" type="xbrli:sharesItemType"/>
  <xs:element id="rytm_NumberOfDaysToExerciseUnderwritingOption" abstract="false" name="NumberOfDaysToExerciseUnderwritingOption" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="rytm_TerminationAgreementMember" abstract="true" name="TerminationAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_RepaymentOfUpfrontFeesOnTermination" abstract="false" name="RepaymentOfUpfrontFeesOnTermination" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_AdditionalConsiderationForShareRepurchase" abstract="false" name="AdditionalConsiderationForShareRepurchase" nillable="true" xbrli:periodType="instant" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_ReversalOfLicenseRevenueRecognizedOnTerminationOfContract" abstract="false" name="ReversalOfLicenseRevenueRecognizedOnTerminationOfContract" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_NetReductionInLicenseRevenueUponTerminationOfContract" abstract="false" name="NetReductionInLicenseRevenueUponTerminationOfContract" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_RevenueInterestFinancingAgreementMember" abstract="true" name="RevenueInterestFinancingAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_RoyaltyInterestFinancingAgreementMember" abstract="true" name="RoyaltyInterestFinancingAgreementMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_DebtCovenantMilestoneAxis" abstract="true" name="DebtCovenantMilestoneAxis" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrldt:dimensionItem" type="xbrli:stringItemType"/>
  <xs:element id="rytm_DebtCovenantMilestoneDomain" abstract="true" name="DebtCovenantMilestoneDomain" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_AnnualNetRevenuesUpTo125MillionMember" abstract="true" name="AnnualNetRevenuesUpTo125MillionMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_AnnualNetRevenuesBetween125MillionAnd300MillionMember" abstract="true" name="AnnualNetRevenuesBetween125MillionAnd300MillionMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_AnnualNetRevenuesExceeding300MillionMember" abstract="true" name="AnnualNetRevenuesExceeding300MillionMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_CumulativeMinimumPaymentsFundingThresholdDateMarch312027Member" abstract="true" name="CumulativeMinimumPaymentsFundingThresholdDateMarch312027Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_CumulativeMinimumPaymentsFundingThresholdDateMarch312029Member" abstract="true" name="CumulativeMinimumPaymentsFundingThresholdDateMarch312029Member" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_ProceedsFromRoyaltyFinancingAgreement" abstract="false" name="ProceedsFromRoyaltyFinancingAgreement" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_PercentOfRoyaltyInterestPaymentOnAnnualNetRevenues" abstract="false" name="PercentOfRoyaltyInterestPaymentOnAnnualNetRevenues" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="rytm_ThresholdAnnualNetRevenuesForRoyaltyInterest" abstract="false" name="ThresholdAnnualNetRevenuesForRoyaltyInterest" nillable="true" xbrli:periodType="duration" xbrli:balance="credit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_ThresholdPercentOfCumulativeMinimumPaymentsFundingToInvestors" abstract="false" name="ThresholdPercentOfCumulativeMinimumPaymentsFundingToInvestors" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="rytm_RevenueInterestsPayableCapAsPercentOfInvestmentAmount" abstract="false" name="RevenueInterestsPayableCapAsPercentOfInvestmentAmount" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:percentItemType"/>
  <xs:element id="rytm_RevenueInterestPaymentPeriodFromInitialClosing" abstract="false" name="RevenueInterestPaymentPeriodFromInitialClosing" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="rytm_DurationMilestonePaymentsNotExpectingToBePaid" abstract="false" name="DurationMilestonePaymentsNotExpectingToBePaid" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:durationItemType"/>
  <xs:element id="rytm_NumberOfBusinessSegments" abstract="false" name="NumberOfBusinessSegments" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="xbrli:integerItemType"/>
  <xs:element id="rytm_SingleReportableSegmentMember" abstract="true" name="SingleReportableSegmentMember" nillable="true" xbrli:periodType="duration" substitutionGroup="xbrli:item" type="dtr-types:domainItemType"/>
  <xs:element id="rytm_PreclinicalClinicalAndDevelopmentExpense" abstract="false" name="PreclinicalClinicalAndDevelopmentExpense" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
  <xs:element id="rytm_CommercialAndMedicalExpenses" abstract="false" name="CommercialAndMedicalExpenses" nillable="true" xbrli:periodType="duration" xbrli:balance="debit" substitutionGroup="xbrli:item" type="xbrli:monetaryItemType"/>
</xs:schema>
