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The pathogenesis of ulcerative colitis (UC) has been fundamentally associated with intestinal microbiota dysbiosis and disruption of immune homeostasis. This study systematically investigates the therapeutic potential of Lactiplantibacillus plantarum HYY-S10 (HYY-S10), a novel strain isolated from De’ang sour tea in Yun an, China, with a focus on its mechanisms for alleviating colitis through the modulation of gut microbiota. Using a dextran sulfate sodium (DSS)-induced colitis model in C57BL/6J mice, our findings demonstrated that seven days of oral supplementation with HYY-S10 (1 × 10⁸ CFU/mL, 0.2 mL/10 g body weight) significantly improved Disease Activity Index (DAI) scores and attenuated characteristic colitis symptoms, including progressive weight loss, rectal bleeding, and abnormal stool consistency. Administration of HYY-S10 exhibited significant immunomodulatory effects characterized by the downregulation of pro-inflammatory mediators (such as IL-1β, IL-6, IFN-γ, and LPS) while concomitantly upregulating anti-inflammatory IL-10 expression. Additionally, the strain enhanced intestinal antioxidant capacity by increasing GSH-Px activity, which collectively contributed to the reduction in intestinal inflammation. Furthermore, HYY-S10 demonstrated multifaceted protective effects by ameliorating oxidative stress through the restoration of redox homeostasis and modulation of gut microbial ecology. Probiotic intervention significantly increased short-chain fatty acids (SCFAs) production and notably enhanced the relative abundance of beneficial taxa, including Akkermansia and Ruminococcus_B, while restoring microbial diversity and ecological stability. Collectively, our results demonstrate that HYY-S10 alleviates experimental colitis by modulating the intestinal immune axis and microbiota composition, providing mechanistic insights to support its potential as a probiotic-based therapeutic strategy for UC. Full article