BACKGROUND AND OBJECTIVES: Few studies have assessed the possible interaction between and impact of IL-6 variants and serum α-tocopherol levels on periodontal condition in older individuals. Here, we assessed the relationship between IL-6 variants and serum α-tocopherol levels on periodontal condition by considering effect modification. MATERIAL AND METHODS: Among the study participants, 359 who were 71 years of age underwent a dental examination, biochemical analysis, and interview. After dividing the participants into tertiles based on serum α-tocopherol levels, we conducted Poisson regression analysis to compare the prevalence rate ratio (PRR) for periodontal disease markers with the IL-6 genotype (rs1800796) based on each tertile adjusted by the number of teeth present (offset). RESULTS: The PRRs of the IL-6 genotype for periodontal condition (probing pocket depth [PPD], clinical attachment level [CAL], and bleeding on probing [BOP]) which were adjusted by the number of teeth present (offset) were 1.17 (P < .001), 1.37 (P < .001), and 1.08 (P = .048), respectively. In addition, a significant association was found between the reciprocal number of PRRs of the IL-6 genotype and three serum α-tocopherol levels. The adjusted PRRs (± standard error) of the IL-6 genotypes for PPD were 0.48 (0.12) for the first group (P < .001), 1.54 (0.04) for the second group (P < .001), and 2.11 (0.03) for the third group (P < .001); similar tendencies were seen for CAL and BOP. CONCLUSION: The results of this study suggest a potential association between the IL-6 genotype and periodontal condition in relation to serum antioxidant concentrations.