OBJECTIVES: Diabetic nephropathy (DN) is a severe complication of diabetes mellitus, and its pathogenesis remains incompletely understood. Emerging evidence suggests a potential link between gut microbiota and DN. This study aimed to explore the causal relationship between gut microbiota and DN using a two-sample Mendelian randomization (MR) approach. METHODS: Gut microbiota data were obtained from the MiBioGen consortium, which provides the most comprehensive genome-wide association studies (GWAS) on gut microbiota. Summary-level genetic data for DN were sourced from publicly available GWAS data provided by the FinnGen consortium. The primary analysis was conducted using the inverse variance-weighted (IVW) method, complemented by sensitivity analyses to evaluate pleiotropy and heterogeneity. RESULTS: Fourteen gut microbiota species demonstrated significant genetic associations with DN in the MR analysis, including five negatively and nine positively associated species, as determined by the IVW method. No evidence of pleiotropy or heterogeneity was observed, ensuring the robustness of the findings. CONCLUSIONS: This study provides novel insight into the causal role of gut microbiota in DN pathogenesis, uncovering specific microbial species that may contribute to disease progression. These findings offer a promising avenue for future research and therapeutic development targeting gut microbiota.