© 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.Objectives: The aim of this study is to investigate the potential role of ANRIL polymorphisms in susceptibility to periodontitis. Methods: The authors searched Pubmed, Web of Science, and Scopus up to April 2021 to identify all published studies without any language restriction on the association between ANRIL and periodontitis. A meta-analysis of all ANRIL variants replicated by three or more studies was performed by testing multiple genetic models of association. Pooled odds ratios and 95% confidence intervals (CI) were used to estimate associations. Tests for sensitivity and publication bias were performed. Results: Twenty-two variants in the ANRIL gene were examined for their potential association with the risk of periodontitis. However, only 4 (rs1333048, rs1333042, rs2891168, rs496892) are replicated at least three or more studies. The ANRIL rs1333048 was the most replicated polymorphisms with five articles, seven different populations comprising of 1331 cases, and 2624 controls. The pooled overall analysis showed that rs1333048, rs1333042, rs2891168, and rs496892 polymorphisms were associated with susceptibility to periodontitis in the whole population in allele contrast and dominant models. Moreover, similar to the overall analysis, rs1333048 polymorphism showed a significant association with grade C periodontitis (known as aggressive periodontitis in 1999 classification) in allele contrast (OR = 1.16) and dominant models (1.19). Interestingly, subgroup analysis also showed rs1333048 polymorphism might influence predisposition to a slowly progressive form of periodontitis (known as chronic periodontitis in 1999 classification). Conclusion: Our findings suggest that the ANRIL rs1333048, rs1333042, rs2891168, and rs496892 polymorphisms might influence predisposition to periodontitis, particularly in Caucasians. Clinical significance: ANRIL gene may represent a potential risk marker for periodontitis.