Background: Chronic periodontitis (CP) is a prevalent inflammatory disease worldwide, characterized by the destruction of periodontal tissue due to an immune response triggered by periodontopathogenic bacteria and the prolonged release of reactive oxygen species (ROS). Excess ROS leads to tissue damage through mechanisms such as lipid peroxidation and DNA damage. The aim of this study was to evaluate oxidative and genotoxic damage by quantifying 8-hydroxy-2-deoxiguanosine (8-OHdG), malondialdehyde (MDA), and nuclear abnormalities (NAs) in individuals with CP. Methods: The participants were divided into a CP group (n = 30) and a control group without CP (n = 30). Saliva was collected to quantify 8-OHdG (via ELISA) and MDA (via spectrophotometry). Buccal mucosa samples were collected to assess NAs. Periodontal parameters, probing depth (PD), clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BOP), were recorded. Results: The levels of 8-OHdG and MDA were significantly higher in the CP group. NAs were also significantly increased. Positive correlations were observed between 8-OHdG, MDA levels and NAs with clinical parameters. Conclusions: The elevated levels of 8-OHdG, MDA and NAs reflect oxidative and genotoxic damage correlated with CP severity. These biomarkers could complement diagnosis, monitor progression, and assess treatment efficacy. Their elevation may also indicate increased systemic disease risk.