The aim is to explore the causal relationship between gluten-free diet and IgA nephropathy by conducting Mendelian randomization (MR) analysis and briefly summarizing the current research on gluten-free diet and IgA nephropathy to provide new insights for the prevention and treatment of IgA nephropathy. The 64,949 samples of gluten-free diet and 477,784 samples of IgA nephropathy were obtained from the genome-wide association study. Four genetic variants strongly associated with a gluten-free diet were extracted as instrumental variables. Two-sample MR analysis was performed by multiplicative random-effects inverse variance weighted, MR-Egger regression, weighted median, weighted mode, simple median, maximum likelihood ratio, and penalized weighted median as analysis models, respectively. Odds ratio values were used to evaluate the causal relationship between gluten-free diet and IgA nephropathy. The sensitivity analysis was carried out by the Cochran Q test, MR-Pleiotropy RESidual Sum and Outlier test, MR-Egger intercept test, and leave-one-out analysis to assess the robustness of the results. Multiplicative random-effects inverse variance weighted analysis showed a significant negative correlation between gluten-free diet and IgA nephropathy (odds ratio = 2.333 × 10-4, 95% confidence interval = 4.628 × 10-6~1.176 × 10-2, P = 2.899 × 10-5). In conclusion, there might be a negative causal relationship between gluten-free diet and IgA nephropathy, which could potentially reduce the risk of IgA nephropathy.