Periodontitis is one of the most typical chronic dental diseases. This inflammatory disease can change various functions of immune cells and impair lipid metabolism through proinflammatory cytokines. High-Density Lipoprotein (HDL) is considered protective of the cardiovascular system. It has anti-thrombotic and anti-inflammatory effects. In this article, we have reviewed the association between periodontitis and HDL. Various studies have demonstrated a reverse relationship between inflammatory cytokines and HDL. HDL contains antioxidative enzymes and proteins, whereas periopathogens impair HDL's antioxidant function. The presence of periodontal bacteria is associated with a low HDL level in patients with periodontitis. Genetic variants in the interleukin-6 (IL)-6 gene and cytochrome (CYP)1A1 rs1048943 gene polymorphism are associated with HDL levels and periodontal status. Studies showed that HDL levels improve after treatment for periodontitis. On the one hand, periodontal pathogenic bacteria and their metabolites and pro-inflammatory cytokines from periodontal infection can result in various disorders of lipid metabolism and lipid peroxidation. On the other hand, hyperlipidemia and lipid peroxidation stimulate proinflammatory cytokines, resulting in oxidative stress and delayed wound healing, making individuals susceptible to periodontitis.