Patients with periodontitis have been found to have higher salivary concentrations of malondialdehyde, a biomarker of lipid hyperoxidation, compared to healthy subjects. However, the association between salivary malondialdehyde levels and periodontitis, independently of other risk factors, has not been analyzed. Therefore, the novel objective of our study was to explore this possible association by performing a logistic regression analysis. This observational, prospective study was carried out in a private dental practice. Salivary malondialdehyde levels were measured in subjects with periodontitis (characterized by periodontal tissue loss) and in subjects without periodontitis (either periodontally healthy or with localized gingivitis in <30% of sites). A multivariate regression analysis was carried out to determine the factors associated with periodontitis. Variables with a -value ≤ 0.05 in the comparison between subjects with and without periodontitis were included in the regression analysis. A total of 119 subjects were included, 63 with periodontitis and 56 without (35 periodontally healthy subjects and 21 patients with localized gingivitis). In the multiple binomial regression analysis, salivary malondialdehyde levels > 0.77 nmol/mL were identified as a predictor of periodontitis ( = 0.03), after controlling for age ( < 0.001), diabetes mellitus ( = 0.81), arterial hypertension ( = 0.43), smoking status (never smoked = 0.08), and cardiovascular disease ( = 0.88). To our knowledge, this is the first study to report that salivary malondialdehyde levels are associated with periodontitis, independently of other known risk factors.