ObjectivesThe purpose of this study was to investigate whether there is a causal relationship between periodontitis and breast cancer by Mendelian randomization analysis.Materials and methodsWe performed a two-sample bidirectional Mendelian randomization (MR) analysis using publicly released genome-wide association studies (GWAS) statistics. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied complementary methods, including weighted median, weighted mode, simple mode, MR-Egger regression, and MR-pleiotropy residual sum and outlier (MR-PRESSO) to detect and correct for the effect of horizontal pleiotropy.ResultsIVW MR analysis showed no effect of periodontitis on breast cancer (IVW OR=0.99,P=0.14). Similarly, no significant causal relationship between breast cancer and periodontitis was found in reverse MR analysis (IVW OR=0.95,P=0.83). The results of MR-Egger regression, weighted median, and weighted mode methods were consistent with those of the IVW method. Based on sensitivity analyses, horizontal pleiotropy is unlikely to distort causal estimates.ConclusionsAlthough observational studies have reported an association between periodontitis and breast cancer, the results of our MR analysis do not support a causal relationship between periodontitis and breast cancer.Clinical relevanceMendelian randomization study can more clearly analyze the causal relationship between periodontitis and breast cancer, in order to provide a certain reference for clinicians and deepen the understanding of the relationship between periodontitis and breast cancer, to explore more possible associations between periodontitis and systemic diseases.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00784-023-04874-x.