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Clinically, RA manifests as joint pain, swelling, and functional impairment caused by persistent synovial inflammation. Additionally, RA can involve vital organs, including the cardiovascular and respiratory systems, thereby significantly compromising patients' quality of life and increasing the risk of disability. In recent years, natural polysaccharides have attracted increasing attention in research on RA prevention and treatment because of their multi\u2010target regulatory effects, high bioactivity, and low\u2010toxicity. Natural polysaccharides can ameliorate the pathological progression of RA through various mechanisms, including modulating immune balance, suppressing inflammatory responses, alleviating oxidative stress, inhibiting the abnormal proliferation of synovial fibroblasts, and regulating gut microbiota. This review systematically summarizes the pharmacodynamic basis and molecular mechanisms underlying the anti\u2010RA effects of natural polysaccharides reported since 2000, with particular emphasis on recent advances in novel drug delivery technologies and a critical evaluation of clinical application studies. These findings aim to provide scientific evidence and theoretical support for developing new therapeutic strategies involving natural polysaccharides for RA treatment.<\/jats:p>","DOI":"10.1002\/ptr.70455","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:52:16Z","timestamp":1789656736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Polysaccharides for Rheumatoid Arthritis Therapy: Mechanism, Drug Delivery and Clinical Application"],"prefix":"10.1002","author":[{"given":"Luxin","family":"Li","sequence":"first","affiliation":[{"name":"Key Laboratory of Basic and Application Research of Beiyao (Heilongjiang University of Chinese Medicine), Ministry of Education  Harbin China"},{"name":"Traditional Chinese Medicine (TCM) Biological Genetics (Heilongjiang Province Double First\u2010Class Construction Interdiscipline)  Harbin 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