Ulcerative colitis (UC) is a leading health challenge worldwide. The evidence of the benefits of gut microbiota metabolites for the treatment of ulcerative colitis is accumulating, but the underlying mechanism remains to be further elucidated. Hence, the aim of this study was to decipher the role of gut microbiota metabolites in the management of UC through employing network pharmacology approach. The targets of gut microbiota metabolites were acquired from gutMgene database, similarity ensemble approach (SEA) and SwissTargetPrediction (STP) respectively. The ulcerative colitis related targets were acquired from GeneCards and DisGeNet database. DAVID platform was used to identify key pathways. Molecular docking was used to assess the binding affinity of metabolites with targets. The final core targets were PPARG, IL6 and AKT1. IL-17 signaling pathway and Toll-like receptor signaling pathway were regarded as critical pathway involved in the development of ulcerative colitis. Equol, Butyrate, Acetate and Propionate were identified as the key metabolites against ulcerative colitis. Molecular docking results demonstrated that Equol displayed strong binding affinity to the core targets. the key gut microbiota metabolites exerted beneficial effects on ulcerative colitis through interacting with multi-targets and multi-pathways, these findings highlighted the potential clinical application of gut microbiota metabolites to the treatment of ulcerative colitis.