BACKGROUND: Previous observational studies have suggested a possible association between periodontal disease and gastric cancer (GC); however, a causal relationship has not yet been established. This study aimed to explore the causal relationship between the 2 through a 2-sample bidirectional Mendelian randomization (MR) study. METHODS: Genome-wide association studies (GWAS) summary statistics were obtained from publicly available GWAS and relevant databases. Two-sample bidirectional MR analysis was conducted to investigate the causal relationship between periodontal disease and GC using the inverse-variance weighted (IVW) method selected as the primary analytical approach. Cochran Q test, MR-PRESSO, MR-pleiotropy, and leave-one-out analyses were performed to assess heterogeneity, pleiotropy, and sensitivity. RESULTS: In European ancestry, IVW analysis revealed no causal relationship between periodontal disease and GC (OR = 1.873; 95% CI [4.788e-10, 7.323e + 09]; P = .956), or between loose teeth and GC (OR = 1.064; 95% CI [0.708, 1.598]; P = .765). In East Asian ancestry, there was no causal relationship between periodontitis and GC according to IVW (OR = 0.948; 95% CI [0.886, 1.015]; P = .126). Conversely, according to the results of the IVW analysis, there was no causal relationship between GC and periodontal disease, regardless of European or East Asian ancestry. Furthermore, there was no heterogeneity or pleiotropy in the causal relationships between these variables (all P > .05), suggesting a certain level of reliability in our results. CONCLUSION: Within the limitations of this MR study, we found no mutual causal relationship between periodontal disease and GC. This finding can prevent overtreatment by clinical physicians and alleviate the psychological burden on patients.