This study evaluates the efficacy of lycopene in the treatment of oral leukoplakia and compares 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 three months. Outcome was assessed clinically as well as histologically. Post-treatment patients were on follow-up for two months. Student's 't' test was used for statistical evaluation. Clinically the patients in Groups A, B, C had a mean response of 80%, 66.25% and 12.5% respectively. Histological evaluation too had similar results. Patients receiving lycopene in both regimes show highly significant difference in response as compared to placebo (Group C). The observed effect of lycopene suggests that it can be effectively and safely used for the management of oral leukoplakia.