Objectives: The aim of this study was to study the effects of periodontitis, diabetes mellitus (DM), and tobacco smoking and chewing habits (TBSCH) on the oxidative stress biomarker levels, namely malondialdehyde (MDA), and the mucosal genotoxic nuclear damage in the marginal gingival cells of subjects. Furthermore, the correlation of the biomarkers, MDA, and nuclear changes in the form of micronucleation (Mn) and binucleation (Bn) was investigated. Materials and Methods: Forty study participants were divided into five subject categories, which were established based on the presence of periodontitis, DM, and TBSCH. Whole saliva and marginal gingival smears collected from subjects were used to determine MDA levels and nuclear changes, respectively. A fullmouth assessment of periodontal pocket depth, clinical attachment loss, and bleeding on probing was performed for each subject to determine periodontal status. Results: MDA and Mn levels between control group and subjects with only periodontitis (MDA: P < 0.9990; Mn: P < 0.8200) showed no significant difference, whereas levels among subjects with DM, TBSCH, and periodontitis, and all other categories were statistically significant (MDA: P < 0.001). DM and/or TBSCH superimposed on periodontitis cause an exponential increase in biomarker levels. Furthermore, MDA and Mn showed poor correlation (r = 0.162; P = 0.318). Periodontitis alone did not significantly increase oxidative stress levels compared to healthy controls, whereas DM and TBSCH resulted in augmented oxidative stress levels, implying that increased stress produced by DM and TBSCH aggravates or exaggerates periodontal inflammation. Conclusion: Poor correlation between MDA and Mn indicated that the mechanisms involved in their production are independent of each other.