Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disorder characterized by complex polygenic inheritance and refractory clinical manifestations. As one of the most challenging gastrointestinal conditions with unclear etiology, UC frequently exhibits persistent mucosal inflammation extending from the rectum to proximal colon regions. The limited efficacy of existing pharmacological regimens, coupled with its recurrent and treatment-resistant progression, highlights an imperative demand for advanced therapeutic innovations targeting this multifactorial pathology. Qing-Chang-Hua-Shi granule (QCHS), a traditional Chinese medicine for the treatment of UC, which has been widely used in clinical practice. Here, it is shown that QCHS improves the inflammatory response and intestinal barrier in DSS-induced colitic mice by regulating gut microbiota and their secreted metabolites. Specifically, QCHS increased the relative abundance of Lactobacillus gasseri ( L. gasseri) and altered the composition of metabolite in feces. Further analysis showed that the metabolites altered by QCHS were significantly enriched in the ferroptosis metabolic pathway. QCHS can also promote the proliferation of L. gasseri in vitro and effectively repair ferroptosis-like injury in the colon of UC mice. Overall, these results indicate that QCHS is an effective agent against UC mainly through the regulation of ferroptosis associated metabolic pathway by modulating Lactobacillus gasseri novelty.