Chronic periodontitis is an infectious disease caused by plaque as the initiating factor. Clinically, it manifests as irreversible loss of hard tissue, leading to the destruction of surrounding periodontal tissue, including the deep periodontal pocket, loss of attachment, and finally, tooth loss. Interleukin-18 (IL-18) can promote inflammation and regulate immune function and plays an important role in mediating the host immune response and inflammatory response. An increase in IL-18 in vivo can induce the production of interferon and inflammatory factors, such as interleukin, tumor necrosis factor and matrix metalloproteinase, thus mediating the dual reaction of immunity and inflammation. These inflammatory factors are involved in the occurrence and development of chronic periodontitis. Many clinical studies have shown that the levels of IL-18 in serum, saliva, gingival crevicular fluid and gingival tissue samples of patients with chronic periodontitis may be positively correlated with the severity of periodontitis; however, as a candidate gene, IL-18 is involved in the susceptibility polymorphism of periodontitis. Understanding how to quantify the level of IL-18 in clinical studies and apply it to diagnostic tools and new sites identified by new methods (genome-wide association studies and omics research) will also deepen our understanding of the pathogenesis of IL-18 in chronic periodontitis and provide new ideas for future precision medicine and the formulation of personalized programs. In this paper, the structure, biological function and association between IL-18 and periodontitis are reviewed.