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Objectives: To assess the association between periodontal disease and Helicobacter pylori (H. pylori) infection in oral cavity., Materials and Methods: We searched PubMed, Embase, Web of Science, Cochrane library, Gray literature, and clinicaltrials.gov for eligible studies up to September 25, 2019. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The random-effects model was used with the software STATA 13.0. The Newcastle-Ottawa-Scale was used for quality evaluation., Results: Twelve observational studies (eight from Asia, one from Europe, and three from the South America) involving 2727 participants were included in the meta-analysis. The overall pooled results showed that H. pylori infection in oral cavity was associated with periodontal disease (OR 2.53, 95% CI 1.86-3.44, P < 0.05). No significant heterogeneity among the articles was observed (I 2  = 44.3%, P < 0.05). The sensitivity analysis indicated that the result of our meta-analysis was generally stable. The Begg test and the Egger test both showed no publication bias was observed (P = 0.45 and P = 0.18 respectively)., Conclusions: Based on current available evidence, it seemed there was a correlation between oral H. pylori infection and the occurrence of periodontal disease. However, since most of the data comes from Asia, more large-scale investigations with high quality from all over the world are needed to confirm the association., Clinical Relevance: H. pylori infection in oral may have a positive association with the prevalence of periodontal disease mainly in Asian populations.