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Although proton pump inhibitors (PPIs) and histamine-2 receptor antagonists are frequently employed to treat GERD, their prolonged administration is associated with adverse effects, necessitating the development of alternative therapeutic strategies. Natural products are now recognized as promising candidates for the management of GERD due to their bioactive compounds, which possess antioxidant, anti-inflammatory, and mucosal-protective properties. The potential of natural products in the treatment of GERD is comprehensively examined in this review, with a focus on their mechanisms of action, which include acid suppression, esophageal mucosal regeneration, anti-inflammatory activity, and gut microbiota modulation. Also, the efficacy and safety of key natural products, including flavonoids, polyphenols, plant-derived oils, herbal extracts, probiotics, and dietary components, in preclinical and clinical studies, are assessed. Additionally, this review addresses the barriers confronting the translation of natural therapies into clinical practice, such as regulatory obstacles, variability in bioavailability, and the need for dosage standardization. The integration of natural products into the management of GERD has the potential to enhance conventional therapies, providing a more comprehensive and secure approach for patients.<\/jats:p>","DOI":"10.3390\/nu17061069","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T06:10:53Z","timestamp":1742364653000},"page":"1069","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Natural Products in the Management of Gastroesophageal Reflux Disease: Mechanisms, Efficacy, and Future Directions"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3319-5863","authenticated-orcid":false,"given":"Kayode","family":"Komolafe","sequence":"first","affiliation":[{"name":"Environmental Science PhD Program, Jackson State University, Jackson, MS 39217, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Titilope","family":"Komolafe","sequence":"additional","affiliation":[{"name":"Environmental Science PhD Program, Jackson State University, Jackson, MS 39217, USA"},{"name":"Department of Biology, Jackson State University, Jackson, MS 39217, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olamide","family":"Crown","sequence":"additional","affiliation":[{"name":"Chemistry and Biotechnology Science and Engineering Programs, The University of Alabama in Huntsville, Huntsville, AL 35899, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basiru","family":"Ajiboye","sequence":"additional","affiliation":[{"name":"Phytomedicine and Molecular Toxicology Research Laboratory, Department of Biochemistry, Federal University Oye Ekiti, Oye Ekiti 370112, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3192-5132","authenticated-orcid":false,"given":"Felicite","family":"Noubissi","sequence":"additional","affiliation":[{"name":"Department of Biology, Jackson State University, Jackson, MS 39217, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ifedayo","family":"Ogungbe","sequence":"additional","affiliation":[{"name":"Chemistry and Biotechnology Science and Engineering Programs, The University of Alabama in Huntsville, Huntsville, AL 35899, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Graham","sequence":"additional","affiliation":[{"name":"Environmental Science PhD Program, Jackson State University, Jackson, MS 39217, USA"},{"name":"Department of Biology, Jackson State University, Jackson, MS 39217, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"ref_1","unstructured":"Antunes, C., Aleem, A., and Curtis, S.A. 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