Abstract Background Periodontitis is closely associated with chronic systemic diseases. Healthy lifestyle interventions have health-enhancing effects on chronic systemic disorders and periodontitis, but the extent to which healthy lifestyle combinations are associated with periodontitis is unclear. Therefore, this study aimed to investigate the association between periodontitis and different healthy lifestyle combinations. Methods 5611 participants were included from the National Health and Nutrition Examination Survey (NHANES, 2009–2014). Six healthy lifestyles factors were defined as fulfilling either: non-smoking, moderate drinking, moderate body mass index (BMI), physical activity, healthy sleep and appropriate total energy intake. Then, the adjusted logistic regression models were performed to identify the association between the periodontitis and the scoring system composed of six lifestyles (0–6 scale). Finally, different scenarios were dynamically and randomly combined to identify the optimal and personalized combination mode. Results Higher healthy lifestyle scores were significantly associated with lower periodontitis prevalence (p
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