The natural compound DMLL alleviates DSS-induced experimental colitis through modulating gut microbiota and metabolic dysbiosis. The phylum of Bacteroidota and genera of norank_f_Muribaculaceae and Ruminococcus with beneficial potential for UC were the major gut flora regulated by DMLL. In terms of microbiota-derived metabolites, DMLL primarily enriched tryptophan metabolites, secondary bile acids and nicotinamide that possess anti-inflammatory activity and proved protection for intestinal epithelial barrier, subsequently altered the metabolic pathways and improved the impaired host gut homeostasis.