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Current therapies mainly rely on anti\u2010resorptive or anabolic agents, which often fail to restore long\u2010term skeletal homeostasis. The gut\u2013bone axis integrates intestinal barrier integrity, immune signaling, microbial metabolism, and bone remodeling, offering substantial therapeutic potential. Translating this insight into clinical strategies remains challenging. Natural polysaccharides, especially from traditional herbal medicines, function not merely as passive carriers but as active nanocarriers capable of modulating the gut\u2013bone axis, highlighting their emerging role beyond conventional drug delivery. Polysaccharide\u2010based nanocarriers integrate drug delivery with intestinal microenvironment modulation through their structural complexity, dynamic interfacial behavior, and prebiotic\u2010like properties, facilitating coordinated regulation of intestinal barrier integrity, immune responses, and microbiota\u2010derived metabolites, offering new avenues for osteoporosis therapy. We summarize how polysaccharide\u2010mediated self\u2010assembly converts noncovalent molecular interactions into biologically responsive delivery behaviors in the intestinal environment, and explore design strategies such as amphiphilic modification, polyelectrolyte complexation, and multicomponent co\u2010assembly to improve the stability, bioavailability, and spatiotemporal activity of herbal small molecules. Beyond pharmacokinetic enhancement, these systems amplify intestinal signaling and transmit immune\u2013metabolic cues to bone, providing promising directions for therapeutic innovation in osteoporosis.<\/jats:p>","DOI":"10.1002\/adhm.71429","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:09:48Z","timestamp":1783400988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Natural Polysaccharide\u2010Mediated Nano\u2010Delivery Systems for Osteoporosis Therapy From a Gut\u2013Bone Axis Regulatory Perspective"],"prefix":"10.1002","volume":"15","author":[{"given":"Ying","family":"Yang","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Pharmacy Affiliated Jiangning Hospital of Chinese Medicine China Pharmaceutical University  Nanjing P. R. 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