Objective: To evaluate the efficacy of systemic lycopene along with routine scaling and root planing in terms of changes in clinical parameters and levels of circulating tumor necrosis factor alpha (TNF-α), salivary interleukin 1beta (IL-1ß), and uric acid in chronic periodontitis. Method and Materials: Forty-two systemically healthy subjects with chronic periodontitis were included in a randomized, placebo-controlled, parallel design, double-blinded trial. The subjects were randomly distributed between the two treatment groups: test group (n = 21) 8 mg lycopene/day and placebo group (n = 21) along with adjunctive scaling and root planing. Patients were monitored at baseline and at 2 months after therapy. Periodontal parameters regarding plaque index (PI), modified gingival index (MGI), bleeding on probing (BOP), clinical attachment level (CAL) gain, and probing pocket depth (PPD) reduction were evaluated and peripheral blood samples and whole saliva were obtained at these points of time to measure the levels of IL-1ß, TNF-α, and uric acid using commercially available kits. Results: Test group (Lycopene) showed better results after therapy compared to the placebo group with reference to PI (P = .004), MGI (P =.002), BOP (P = .021), salivary IL-1ß (P = .05), and uric acid levels (P = .02). The CAL gain, PPD reduction and serum TNF-α value were not statistically significant but showed an improvement compared to the placebo group. Conclusion: Further longitudinal studies are required to establish the role of lycopene in the management of chronic periodontitis. Keywords: antioxidants, clinical trial, chronic periodontitis, lycopene