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      <submissionType>144</submissionType>
      <filerInfo>
        <filer>
          <filerCredentials>
            <cik>0001563422</cik>
            <ccc>XXXXXXXX</ccc>
          </filerCredentials>
        </filer>
        <liveTestFlag>LIVE</liveTestFlag>
  
  
  
      </filerInfo>
    </headerData>
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      <issuerInfo>
        <issuerCik>0001682639</issuerCik>
        <issuerName>HYPERION DEFI, INC.</issuerName>
        <secFileNumber>001-38365</secFileNumber>
        <issuerAddress>
          <com:street1>23461 SOUTH POINTE DRIVE,</com:street1>
          <com:street2>SUITE 390</com:street2>
          <com:city>LAGUNA HILLS</com:city>
          <com:stateOrCountry>CA</com:stateOrCountry>
          <com:zipCode>92653</com:zipCode>
        </issuerAddress>
        <issuerContactPhone>833-393-6684</issuerContactPhone>
        <nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>MATHER CHARLES E IV</nameOfPersonForWhoseAccountTheSecuritiesAreToBeSold>
        <relationshipsToIssuer>
          <relationshipToIssuer>Director</relationshipToIssuer>
        </relationshipsToIssuer>
      </issuerInfo>
      <securitiesInformation>
        <securitiesClassTitle>Common</securitiesClassTitle>
        <brokerOrMarketmakerDetails>
          <name>Fidelity Brokerage Services LLC</name>
          <address>
            <com:street1>245 Summer Street</com:street1>
            <com:city>Boston</com:city>
            <com:stateOrCountry>MA</com:stateOrCountry>
            <com:zipCode>02110</com:zipCode>
          </address>
        </brokerOrMarketmakerDetails>
        <noOfUnitsSold>1362</noOfUnitsSold>
        <aggregateMarketValue>17515.00</aggregateMarketValue>
        <noOfUnitsOutstanding>2882808</noOfUnitsOutstanding>
        <approxSaleDate>07/22/2025</approxSaleDate>
        <securitiesExchangeName>NASDAQ</securitiesExchangeName>
      </securitiesInformation>
      <securitiesToBeSold>
        <securitiesClassTitle>Common</securitiesClassTitle>
        <acquiredDate>09/18/2018</acquiredDate>
        <natureOfAcquisitionTransaction>Open Mkt Purchase</natureOfAcquisitionTransaction>
        <nameOfPersonfromWhomAcquired>Public Market</nameOfPersonfromWhomAcquired>
        <isGiftTransaction>N</isGiftTransaction>
        <amountOfSecuritiesAcquired>12</amountOfSecuritiesAcquired>
        <paymentDate>09/18/2018</paymentDate>
        <natureOfPayment>Open market</natureOfPayment>
      </securitiesToBeSold>
      <securitiesToBeSold>
        <securitiesClassTitle>Common</securitiesClassTitle>
        <acquiredDate>09/19/2018</acquiredDate>
        <natureOfAcquisitionTransaction>Open Mkt Purchase</natureOfAcquisitionTransaction>
        <nameOfPersonfromWhomAcquired>Public Market</nameOfPersonfromWhomAcquired>
        <isGiftTransaction>N</isGiftTransaction>
        <amountOfSecuritiesAcquired>37</amountOfSecuritiesAcquired>
        <paymentDate>09/19/2018</paymentDate>
        <natureOfPayment>Public Market</natureOfPayment>
      </securitiesToBeSold>
      <securitiesToBeSold>
        <securitiesClassTitle>Common</securitiesClassTitle>
        <acquiredDate>05/28/2021</acquiredDate>
        <natureOfAcquisitionTransaction>Open Mkt Purchase</natureOfAcquisitionTransaction>
        <nameOfPersonfromWhomAcquired>Public Market</nameOfPersonfromWhomAcquired>
        <isGiftTransaction>N</isGiftTransaction>
        <amountOfSecuritiesAcquired>37</amountOfSecuritiesAcquired>
        <paymentDate>05/28/2021</paymentDate>
        <natureOfPayment>Open market</natureOfPayment>
      </securitiesToBeSold>
      <securitiesToBeSold>
        <securitiesClassTitle>Common</securitiesClassTitle>
        <acquiredDate>11/01/2021</acquiredDate>
        <natureOfAcquisitionTransaction>Open Mkt Purchase</natureOfAcquisitionTransaction>
        <nameOfPersonfromWhomAcquired>Public Market</nameOfPersonfromWhomAcquired>
        <isGiftTransaction>N</isGiftTransaction>
        <amountOfSecuritiesAcquired>49</amountOfSecuritiesAcquired>
        <paymentDate>11/01/2021</paymentDate>
        <natureOfPayment>Open Market</natureOfPayment>
      </securitiesToBeSold>
      <securitiesToBeSold>
        <securitiesClassTitle>Common</securitiesClassTitle>
        <acquiredDate>03/31/2022</acquiredDate>
        <natureOfAcquisitionTransaction>Open Mkt Purchase</natureOfAcquisitionTransaction>
        <nameOfPersonfromWhomAcquired>Public Market</nameOfPersonfromWhomAcquired>
        <isGiftTransaction>N</isGiftTransaction>
        <amountOfSecuritiesAcquired>49</amountOfSecuritiesAcquired>
        <paymentDate>03/31/2022</paymentDate>
        <natureOfPayment>Open Market</natureOfPayment>
      </securitiesToBeSold>
      <securitiesToBeSold>
        <securitiesClassTitle>Common</securitiesClassTitle>
        <acquiredDate>05/18/2022</acquiredDate>
        <natureOfAcquisitionTransaction>Open Mkt Purchase</natureOfAcquisitionTransaction>
        <nameOfPersonfromWhomAcquired>Public Marekt</nameOfPersonfromWhomAcquired>
        <isGiftTransaction>N</isGiftTransaction>
        <amountOfSecuritiesAcquired>87</amountOfSecuritiesAcquired>
        <paymentDate>05/18/2022</paymentDate>
        <natureOfPayment>Open Market</natureOfPayment>
      </securitiesToBeSold>
      <securitiesToBeSold>
        <securitiesClassTitle>Common</securitiesClassTitle>
        <acquiredDate>05/15/2023</acquiredDate>
        <natureOfAcquisitionTransaction>Open Mkt Purchase</natureOfAcquisitionTransaction>
        <nameOfPersonfromWhomAcquired>Public Market</nameOfPersonfromWhomAcquired>
        <isGiftTransaction>N</isGiftTransaction>
        <amountOfSecuritiesAcquired>49</amountOfSecuritiesAcquired>
        <paymentDate>05/15/2023</paymentDate>
        <natureOfPayment>Open Market</natureOfPayment>
      </securitiesToBeSold>
      <securitiesToBeSold>
        <securitiesClassTitle>Common</securitiesClassTitle>
        <acquiredDate>05/26/2023</acquiredDate>
        <natureOfAcquisitionTransaction>Open Mkt Purchase</natureOfAcquisitionTransaction>
        <nameOfPersonfromWhomAcquired>Public Market</nameOfPersonfromWhomAcquired>
        <isGiftTransaction>N</isGiftTransaction>
        <amountOfSecuritiesAcquired>37</amountOfSecuritiesAcquired>
        <paymentDate>05/26/2023</paymentDate>
        <natureOfPayment>Open market</natureOfPayment>
      </securitiesToBeSold>
      <securitiesToBeSold>
        <securitiesClassTitle>Common</securitiesClassTitle>
        <acquiredDate>06/17/2025</acquiredDate>
        <natureOfAcquisitionTransaction>Stock Award</natureOfAcquisitionTransaction>
        <nameOfPersonfromWhomAcquired>Issuer</nameOfPersonfromWhomAcquired>
        <isGiftTransaction>N</isGiftTransaction>
        <amountOfSecuritiesAcquired>1000</amountOfSecuritiesAcquired>
        <paymentDate>06/17/2025</paymentDate>
        <natureOfPayment>Compensation</natureOfPayment>
      </securitiesToBeSold>
      <nothingToReportFlagOnSecuritiesSoldInPast3Months>Y</nothingToReportFlagOnSecuritiesSoldInPast3Months>
      <noticeSignature>
        <noticeDate>07/22/2025</noticeDate>
        <signature>/s/ Heather Foxworth as a duly authorized representative of Fidelity Brokerage Services LLC, as attorney-in-fact for MATHER CHARLES E IV</signature>
      </noticeSignature>
    </formData>
  </edgarSubmission>
metadata_documents: [{"type": "144", "sequence": "1", "filename": "primary_doc.xml", "secsgml_size_bytes": 7163}]
text: 144
  0001563422
  XXXXXXXX
  LIVE
  0001682639
  HYPERION DEFI, INC.
  001-38365
  23461 SOUTH POINTE DRIVE,
  SUITE 390
  LAGUNA HILLS
  CA
  92653
  833-393-6684
  MATHER CHARLES E IV
  Director
  Common
  Fidelity Brokerage Services LLC
  245 Summer Street
  Boston
  MA
  02110
  1362
  17515.00
  2882808
  07/22/2025
  NASDAQ
  Common
  09/18/2018
  Open Mkt Purchase
  Public Market
  N
  12
  09/18/2018
  Open market
  Common
  09/19/2018
  Open Mkt Purchase
  Public Market
  N
  37
  09/19/2018
  Public Market
  Common
  05/28/2021
  Open Mkt Purchase
  Public Market
  N
  37
  05/28/2021
  Open market
  Common
  11/01/2021
  Open Mkt Purchase
  Public Market
  N
  49
  11/01/2021
  Open Market
  Common
  03/31/2022
  Open Mkt Purchase
  Public Market
  N
  49
  03/31/2022
  Open Market
  Common
  05/18/2022
  Open Mkt Purchase
  Public Marekt
  N
  87
  05/18/2022
  Open Market
  Common
  05/15/2023
  Open Mkt Purchase
  Public Market
  N
  49
  05/15/2023
  Open Market
  Common
  05/26/2023
  Open Mkt Purchase
  Public Market
  N
  37
  05/26/2023
  Open market
  Common
  06/17/2025
  Stock Award
  Issuer
  N
  1000
  06/17/2025
  Compensation
  Y
  07/22/2025
  /s/ Heather Foxworth as a duly authorized representative of Fidelity Brokerage Services LLC, as attorney-in-fact for MATHER CHARLES E IV