Previous studies showed thatDEFB1gene polymorphisms may impact the development and progression of periodontitis; nevertheless, inconsistent conclusions were described. This study meta-analytically explored the association between periodontitis theDEFB1 gene polymorphisms and periodontitis. We searched PubMed, Embase, Springer and Cochrane Library for the relevant case-control studies of periodontitis up to February 13th, 2019. Two reviewers selected studies according to the predefined inclusion and exclusion criteria. Newcastle-Ottawa Scale (NOS) was used to assess the quality of studies, and the combined effect size was calculated using R 3.12 software. A total of 9 studies involving 4113 patients and 2373 controls were included. Meta-analysis ofDEFB1-G1654A gene polymorphisms showed that there were significant differences in model Avs.G (OR = 3.7876, 95%CI = 2.9051-4.9382,P< 0.001), AAvs.GG (OR = 4.6743, 95%CI = 3.0900-7.0710,P< 0.001), AAvs.GG+AG (OR = 3.5131, 95%CI = 2.4496-5.0384,P< 0.001), AA + AGvs.GG (OR = 4.3087, 95%CI = 2.8827-6.4402,P< 0.001) and AGvs.GG (OR = 3.0639, 95%CI = 1.6804-5.5863,P= 0.003). However, no significant differences were found betweenDEFB1 rs11362, rs1799946 and rs1800972 and periodontitis. Sensitivity analysis implied that our results were robust and no publication bias was noticed. Our meta-analysis showed that theDEFB1-G1654A polymorphism may be a genetic susceptibility factor for periodontitis.