ABSTRACT Quercetin, a natural flavonoid in traditional Chinese medicinal plants, has shown promise in alleviating ulcerative colitis symptoms despite uncertainties about its exact mode of action. This study explored how quercetin influences tryptophan breakdown and gut bacterial populations in mice with chemically induced colitis. The treatment demonstrated measurable improvements—normalizing body weight, reducing spleen enlargement, lowering clinical severity scores, preserving colon structure, and healing tissue damage. Through advanced microbiome profiling and metabolic analysis, researchers observed increased populations of helpful gut microbes alongside higher concentrations of tryptophan byproducts. These biochemical shifts stimulated the aryl hydrocarbon receptor system, which plays a key role in restoring gut lining integrity. The collective evidence points to quercetin’s therapeutic potential through its dual action on microbial ecology and tryptophan-derived signaling pathways. IMPORTANCE Ulcerative colitis is a chronic inflammatory disease with limited effective therapeutic options. In this study, quercetin—a flavonoid commonly found in traditional Chinese medicinal herbs—was shown to relieve colitis symptoms by reshaping gut microbiota and restoring tryptophan metabolism. Notably, the increase in indolelactic acid, a key microbial metabolite, led to activation of the aryl hydrocarbon receptor, which supports intestinal barrier integrity and dampens inflammation. These findings reveal a gut microbiota-derived metabolite-host signaling axis as a central mechanism of action, highlighting the potential of quercetin as a microbiota-targeted therapeutic approach for UC.