The aim of this study was to determine whether tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) promoter polymorphisms confer susceptibility to periodontitis in ethnically different populations. A literature search was performed using PubMed and Embase and a meta-analysis of the identified studies was conducted to explore the associations between TNF-α -308 A/G, -238 A/G, IL-6 promoter -174 G/C and -572 G/C polymorphisms and periodontitis. Seventeen comparison studies for the TNF-α -308 A/G polymorphism and three studies for the TNF-α -238 A/G polymorphism were included in the meta-analysis. And 16 separate studies for the IL-6 -174 G/C polymorphism and 10 studies for the IL-6 -572 G/C polymorphism were considered in our meta-analysis. Analysis after stratification by ethnicity indicated that the TNF-α -308 A allele was associated with periodontitis in Brazilian, Asian, and Turkish populations (OR=0.637, 95% CI=0.447-0.907, p=0.013; OR=0.403, 95% CI=0.204-0.707, p=0.009; OR=1.818, 95; % CI=1.036-3.189, p=0.037). The meta-analysis showed no association between the TNF-α -238 A/G polymorphism and periodontitis. The meta-analysis indicated an association of the IL-6 -174 G/C polymorphisms with periodontitis in Brazilian populations (OR for GG+GC=2.394, 95% CI=1.081-5.302, p=0.031). Stratification by ethnicity and disease type indicated an association between the IL-6 -572 G allele and chronic periodontitis (OR=1.585, 95 % CI=1.030-2.439, p=0.036), and periodontitis in Europeans (OR=2.118, 95% CI=1.254-3.577, p=0.005). This meta-analysis demonstrates that the TNF-α -308 A/G polymorphism confers susceptibility to periodontitis in Brazilian, Asian and Turkish populations. The IL-6 -174 G/C polymorphism may confer susceptibility to periodontitis in Brazilians, and the IL-6 -572 G/C polymorphism may be associated with susceptibility to periodontitis in Europeans, and chronic periodontitis.