PURPOSE-: This study aimed to examine the association between periodontitis and diabetes mellitus. METHODS: Participants with natural teeth in one jaw from the Third United States National Health and Nutrition Examination Survey (1988-1994) were included in this analysis. Participants with moderate (> 4mm attachment loss in ≥ 2 mesial sites or 5mm pocket depth in ≥ 2 mesial sites) or severe (> 6mm attachment loss in ≥ 2 mesial sites and > 5mm pocket depth in ≥ 1 mesial site) periodontitis were classified as having periodontal disease. The rest of the participants were considered without periodontal disease. Diabetes mellitus was defined as fasting glucose ≥ 126mg/dL, hemoglobin A1c ≥ 6.5% or the use of antihyperglycemic medications. Multivariable logistic regression was used to examine the association between periodontitis and diabetes mellitus in all study population and subgroups stratified by demographics and comorbidities. RESULTS: This analysis included 13,000 participants [mean age 43.8 ± 19.1 years, 47.5% male, 30% whites]. About 12.7% (n = 1,656) of the study population had periodontitis, and 9.2% (n = 1,200) had diabetes. In a multivariable-adjusted model, presence (vs. absence) of periodontitis was associated with 66% increased odds of diabetes (OR (95% CI):1.66 (1.43-1.94); p < 0.001). Compared to those without periodontitis, the odds of diabetes among those with severe periodontitis was much higher (OR (95% CI): 2.31(1.72-3.11); p < 0.001) than in those with moderate periodontitis (OR (95% CI): 1.54(1.30-1.82); p < 0.001). CONCLUSIONS: Periodontitis is associated with prevalent diabetes in a dose-response fashion, suggesting a bidirectional relationship between those two diseases. Patients with periodontal disease should be counseled regarding their elevated risk of diabetes. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-022-01010-6.