Pyroptosis is widely involved in many diseases, including periodontitis. Nonetheless, the functions of pyroptosis-related genes (PRGs) in periodontitis are still not fully elucidated. Therefore, we aimed to investigate the role of PRGs in periodontitis. Three datasets (GSE10334, GSE16134, and GSE173078) from the Gene Expression Omnibus (GEO) were selected to analyze the differences in expression values of the PRGs between nonperiodontitis and periodontitis tissue samples using difference analysis. Following this, five hub PRGs (charged multivesicular body protein 2B, granzyme B, Z-DNA-binding protein 1, interleukin-1β, and interferon regulatory factor 1) predicting periodontitis susceptibility were screened by establishing a random forest model, and a predictive nomogram model was constructed on the basis of these genes. Decision curve analysis suggested that the PRG-based predictive nomogram model could provide clinical benefits to patients. Three distinct PRG patterns (cluster A, cluster B, and cluster C) in the periodontitis samples were revealed according to the 48 significant PRGs, and the difference in the immune cell infiltration among the three patterns was explored. We observed that all infiltrating immune cells, except type 2 T helper cells, differ significantly among the three patterns. To quantify the PRG patterns, the PRG score was calculated by principal component analysis. According to the results, cluster B had the highest PRG score, followed by cluster A and cluster C. In conclusion, PRGs significantly contribute to the development of periodontitis. Our study of PRG patterns might open up a new avenue to guide individualized treatment plans for patients with periodontitis.