Background <p>To investigate the association between the Zhejiang University (ZJU) Index, a comprehensive metabolic indicator, and the prevalence of periodontitis in a large-scale population-based study using data from the National Health and Nutrition Examination Survey (NHANES).</p> Methods <p>This cross-sectional study analyzed data from NHANES (2009–2014) and included 7,547 participants after applying strict inclusion and exclusion criteria. The ZJU Index was used as the exposure variable, and periodontitis was diagnosed based on clinical attachment loss and probing pocket depth. Weighted multivariable logistic regression analysis was performed to assess the relationship between the ZJU Index and periodontitis, adjusting for potential confounders. Subgroup and sensitivity analyses were conducted to evaluate the robustness of the findings.</p> Results <p>A significant positive association was found between the ZJU Index and the prevalence of periodontitis, presenting a J-shaped, non-linear relationship (<i>P</i> for nonlinearity = 0.026). When the ZJU Index was ≥ 45, the likelihood of periodontitis increased significantly, and the dose–response curve became steeper. An increase of 5 units in the ZJU Index was associated with an OR of 1.19 for periodontitis (95% CI: 1.02–1.40, <i>P</i> = 0.028). Subgroup analyses showed no significant interactions among different subgroups. Sensitivity analyses confirmed the robustness of the results, with the E-value indicating that the association was robust unless the OR of an unmeasured confounder exceeded 2.17.</p> Conclusions <p>This study confirmed the significant association between the ZJU Index and periodontitis, reinforcing the link between metabolic syndrome and oral health. The ZJU Index may serve as a potential biomarker for early screening assessment of periodontitis. Future research should focus on longitudinal studies to establish causality and evaluate the impact of targeted metabolic interventions on periodontal health.</p>