Interleukin 6 (IL-6) and C-Reactive Protein (CRP) play an important role in chronic periodontitis with coronary artery disease (CAD). Genetic factors can affect a person’s risk of CAD, which affects one-third of the population. This study investigated the role ofIL-6 -572 C/G,CRP -757 A/G, andCRP -717 T/Cgene polymorphisms. IL-6 and CRP levels on the severity of periodontitis in CAD in Indonesia were also evaluated. This case-control study was conducted with mild and moderate–severe chronic periodontitis groups. A path analysis test was conducted with Smart PLS with a 95% confidence interval to determine the significant variable for chronic periodontitis. Our study revealed that the effects ofIL-6 -572 C/G,CRP -757 A/G, andCRP -717 T/Cgene polymorphisms on IL-6 levels and CRP levels were not significant. IL-6 and CRP levels were not significantly different between the two groups. We found that IL-6 levels had a significant effect on CRP levels in periodontitis patients with CAD (path coefficient 0.322,p= 0.003).IL-6 -572 C/G,CRP -757 A/G, andCRP -717 T/Cgene polymorphisms had no effect on the severity of chronic periodontitis in CAD patients in the Indonesian population. We also observed no apparent effects of the influence of gene polymorphisms inIL-6 -572 C/G,CRP -757 A/G, andCRP -717 T/Cgenes. Although the IL-6 and CRP levels were not significantly different between the two groups, IL-6 levels affected CRP levels in periodontitis patients with CAD.