Background Periodontitis is a high prevalence disease, affecting up to 80% of the world's population. Recently studies have shown a connection between periodontal disease and cardiovascular disease, as oxidative stress plays an important role in chronic inflammatory diseases such as periodontal disease and cardiovascular disease. Nuclear factor erythroid 2 -related factor 2 (Nrf2) is the core transcriptional regulator of endogenous antioxidant system and plays a cellular defense role in antioxidant, anti-inflammatory and immune response. Objective To explore Nrf2/antioxidant responsive element (ARE) signaling pathway in periodontitis or periodontitis complicated with atherosclerosis. Method With "Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2), Periodontitis, Atherosclerosis, Oxidative Stress" as the search terms, the authors searched related articles published during 2016-2021 in PubMed, CNKI, Science Direct and other databases by computer, and made the following review through screening, induction and summary. Result & Conclusion Nrf2/ARE signaling pathway is one of the important mechanisms connecting chronic periodontitis and atherosclerosis. Nrf2 can slow down the occurrence and development of periodontitis by promoting osteoblast differentiation, inhibiting osteoclast activation, regulating mesenchymal stem cell proliferation, differentiation and apoptosis. However, inhibition of Nrf2/ARE signaling pathway may increase the risk of periodontitis with atherosclerosis by destroying the integrity of vascular endothelium, increasing lipid accumulation and promoting inflammation.