Primary sclerosing cholangitis (PSC) is a type of chronic idiopathic liver disease characterized by bile duct inflammation and concentric fibrosis. Currently, no drug therapy can change the natural progression of PSC. The mechanism by which PSC is accompanied by the occurrence of inflammatory bowel disease (IBD) is still unclear. Oral antibiotic therapy with vancomycin being the most widely used has been shown to be effective for PSC combined with IBD. This paper analyzes case reports and clinical studies on the use of vancomycin in PSC, with the aim of providing a reference for clinical therapy and in-depth exploration of novel therapeutic directions.