To date, evidence on the relationship between H. pylori infection and biliary diseases remains unclear. This Mendelian randomization (MR) study aim to investigate the causal relationship between H. pylori infection and various biliary system diseases. We obtained summary statistics for 7 hours. Pylori antibody levels and 5 biliary system diseases (cholelithiasis, cholecystitis, biliary system cancers, primary biliary cholangitis, and primary sclerosing cholangitis [PSC]) from public databases of different populations. The 2-sample bidirectional MR analysis was conducted using the Inverse-Variance Weighted (IVW) method, complemented by Bayesian Weighted MR. Heterogeneity analyses, tests for horizontal pleiotropy, and leave-one-out sensitivity analyses were performed to enhance the reliability and stability of the results. This study provided evidence for a causal relationship between H. pylori infection and cholelithiasis, biliary system cancers, and PSC (IVW, P < .05). However, no causal relationship was found between H. pylori infection and cholecystitis or primary biliary cholangitis (IVW, P > .05). Notably, the bidirectional MR analysis provided evidence of reciprocal causal relationships, with genetic liability to cholelithiasis, biliary tract cancer, and PSC likewise showing causal effects on H. pylori infection (IVW, P < .05). This study suggested a causal link between H. pylori infection and various biliary system diseases, discussing their intricate interplay. These findings are significant for advancing our understanding of H. pylori exposure and its role in the pathogenesis of biliary system diseases.