Aim of the study: Comparative evaluation of the efficacy of oral melatonin in combination with oral tranexamic acid (TXA) versus the use of oral TXA alone in the management of melasma. Materials and methods: An in vivo, prospective, randomized, clinical study was conducted to compare and evaluate the efficacy of oral melatonin with oral tranexamic acid (TXA) as a combination therapy versus the use of Oral TXA alone in the management of melasma. Out of 20 patients selected, 10 patients were treated with a combination of oral melatonin and oral TXA (Group A). The remaining 10 patients were treated with oral TXA alone (Group B). Modified Melasma Area and Severity Index (MMASI) was used to assess the treatment outcomes of both the groups before starting the treatment and after every 15 days for 3 months. Result: The P value of <.05 showed that the study results were significant. It indicated a definite statistical difference between the 2 groups. Group A showed a steep unanticipated improvement in the severity score from day 15 to 2 months. Followed by sudden decrease in the severity score from 2 months to day 75 and a gradual decrease up to 3 months. On the contrary, Group B (oral TXA) showed not much improvement till day 15, followed by a slow improvement in 2 months. After 2 months, Group B showed gradual reduction in the severity score up to 3 months. Conclusion: Oral melatonin has an antioxidative property and its use along with oral TXA in the management of melasma gave better results. There was a substantial difference in the severity scores between the 2 groups, demonstrating that using oral TXA alone did not produce as good results as using it in conjunction with oral melatonin.