Therefore, the main objective of this study was to investigate the association between the MTHFR rs1801133 and the DNMT3B rs2424913 polymorphisms, and methylation profiles from MTHFR, miR-9-1, miR-9-3, superoxide dismutase (SOD1), and catalase (CAT) genes with periodontitis. The gene discussed is DNMT3B; the disease is periodontitis.