This study evaluated the efficacy of lycopene in the treatment of oral leukoplakia and compared two different doses with a placebo. Fifty-eight clinically and histologically diagnosed patients of oral leukoplakia were selected for the study. They were randomly divided into three groups. Group A (n = 20) 8 mg lycopene/day, Group B (n = 20) 4 mg lycopene/day and Group C (n = 18) placebo. The duration of the therapy was 3 months. Outcome was assessed clinically as well as histologically. Post-treatment patients were on follow-up for 2 months. Clinically the patients in Groups A, B and C had mean responses of 80, 66.25 and 12.5%, respectively. Histological evaluation had similar results. Patients receiving lycopene in both regimes show a highly significant difference in response as compared to placebo (Group C).