Background and Aim: Oral submucous fibrosis (OSMF) is a high-risk premalignant condition largely seen in the Indian subcontinent. A number of studies have proven the use of antioxidants in the management of OSMF. Therefore, the aim of the present study was to compare the efficacy of two antioxidants, lycopene and aloe vera in the management of OSMF. Material and Methods: One hundred and twenty clinicopathologically diagnosed OSMF patients, were included in the study. They were divided equally into, Group A (lycopene group) and Group B (aloe vera group). Group A was administered 8mg lycopene in two divided doses of 4mg daily and Group B was given5mg aloe vera gel to be applied topically thrice daily for 3 months. Different clinical parameters were evaluated at regular intervals and data was analyzed using the Student's paired t-test and Chi-square test. P < 0.001 was considered to be statistically significant. Results: Clinical improvements in mouth opening and tongue protrusion were significant in Group A (P < 0.001). Subjective symptoms of burning sensation (P = 0.007), pain associated with the lesion (P = 0.005), and difficulty in swallowing and speech (P = 0.003) improved in both the groups, but were insignificant. There was a mild to moderate decrease in the size of the lesion. Conclusion: The present study concludes that though, there is no definitive treatment for the condition; however, lycopene can bring about significant clinical improvements in the symptoms like mouth opening and tongue protrusion when compared to aloe vera. Both the drugs appear to be promising in the treatment of OSMF.