Background: Periodontal disease is a very common observation among dental patients these days. Till date, no study has been done correlating the levels of serum catalase and glutathione peroxidase among chronic periodontitis patients who are tobacco chewers. Purpose: To find a relationship between catalase and glutathione-peroxidase levels in Chronic Periodontitis (CP) patients who are non-tobacco users, smokers and smokeless tobacco (gutkha) users & periodontally healthy subjects. Materials and Methods: This cross-sectional study included 120 subjects ranging in age from 18 to 60 years. Participants were divided into four groups: 30 healthy subjects (H) (group-A), 30 subjects with chronic periodontitis (CP)(Group-b), 30 smokers with CP (CPS)(Group-c) and 30 smokeless tobacco users with CP (CPSTP)(Group-d). The clinical parameters included pocket probing depth (PPD), clinical attachment level (CAL) & gingival index (GI). Catalase (CAT) and glutathione peroxidase (GPx) levels were estimated using UV-spectrophotometry, and the data were analyzed using SPSS software, Mann-Whitney U test and Pearson correlation coefficient tests. Results: Higher serum levels of CAT and GPx (an antioxidant parameter) were found in healthy subjects as compared to periodontitis subjects who were gutkha chewers and smokers. Pairwise comparison by the Mann-Whitney U test showed a significant difference in the mean levels of GPx among all groups (p < 0.05). The mean serum levels of CAT were significantly lower in group (b) as compared to other groups (b