Ulcerative colitis (UC) involves epithelial injury, gut microbial dysbiosis, disturbed microbial metabolism, and mucosal inflammation. This study evaluated the protective effect of Schisandra chinensis (SC) against dextran sulfate sodium (DSS)-induced UC and investigated the underlying microbiota–metabolite–host signaling mechanism. UPLC-Q-TOF-MS/MS identified 38 constituents in SC, predominantly lignans, organic and phenolic acids, and terpenoids. SC reduced body weight loss, disease activity, colon shortening, mucosal and histological injury, and pro-inflammatory cytokine levels, while partially restoring claudin-1 and occludin expression. Metagenomic analysis showed that SC restructured the DSS-disrupted microbiota, enriched Parabacteroides goldsteinii, and increased the predicted abundance of pathways related to valine, leucine, and isoleucine degradation. Untargeted metabolomics and targeted fatty acid analysis showed lower fecal leucine and higher isovalerate levels after SC treatment. Whole-colon transcriptomic and western blot analyses further demonstrated that SC suppressed the mTOR/HIF-1α/STAT3/IL-17 inflammatory program in colonic tissue. Antibiotic pretreatment weakened several protective effects of SC, whereas P. goldsteinii or sodium isovalerate administration partially recapitulated its anti-inflammatory and barrier-restorative effects. Conversely, the mTOR activator MHY1485 attenuated SC-mediated protection. These findings indicate that the protective effects of SC are associated with remodeling of a P. goldsteinii-related leucine–isovalerate metabolic network and attenuation of colonic mTOR/HIF-1α/STAT3/IL-17 signaling. This study provides a microbiota-centered mechanistic basis for the therapeutic potential of SC in UC.