Background <p>There is currently evidence supporting an association between periodontitis and prostate disease, but further research is needed to establish a causal relationship due to potential confounding factors and uncertainty about the direction of causality. The present study employs a bidirectional Mendelian Randomization (MR) analysis to eliminate confounding factors at the genetic level and determine the causal relationship between periodontitis and prostate diseases.</p> Methods <p>Summary data for periodontitis were obtained from the GLIDE consortium (<i>N</i> = 45,563), while data for prostate diseases, including benign prostatic hyperplasia (<i>N</i> = 163,095), prostatitis (<i>N</i> = 134,299), and prostate cancer (<i>N</i> = 146,465), were sourced from the FinnGen database. Various methods were employed in the Mendelian randomization (MR) analysis, including the inverse variance-weighted (IVW) method, MR-Egger regression, weighted median, and weighted mode. Sensitivity analyses, such as the MR-Egger intercept test and MR-PRESSO method, were performed to ensure the reliability and robustness of the results.</p> Results <p>Results from the bidirectional MR analysis using the IVW method as the primary approach, indicate that no causal relationship exists between periodontitis and prostate disease. Consequently, there is insufficient evidence to substantiate their association. Moreover, additional sensitivity analyses performed further reinforce the robustness of our findings.</p> Conclusion <p>Our MR study did not identify a causal relationship between periodontitis and prostate disease. However, we do not rule out the possibility of an underlying etiological connection and shared mechanisms between the two conditions. Therefore, further large-scale studies using various approaches are needed to explore their association in greater depth and provide more comprehensive and accurate guidance for clinical practice.</p>