Background. Melasma is a pigmentary disorder often recalcitrant to treatment. Few studies have objectively evaluated the efficacy of treatment colorimetrically. Aim. To evaluate the safety and efficacy of a depigmentation cream, including mainly glycolic acid and Rumex occidentalis. Method. Twenty-seven patients applied the cream twice daily for the first 3 months and twice weekly for the following 3 months. L*, C* and h* values of the target lesions and the perilesional area were analyzed at baseline, 12 and 24 weeks colorimetrically. The physician and patient evaluated the clinical response rate. These results were compared statistically between the lesional and perilesional area. Results. There was a significant difference between 0-12, 0-24 (L*, C* and h* values) and 12-24 weeks (L* value) (p < 0.001). For C* and h* values, the difference was not significant between 12 and 24 weeks (p = 0.464 and 0.151, respectively). Statistical significance was detected only between 3 and 6 months for C* value (p < 0.05) for the lesional and the perilesional areas. Clinical response rate was significant (p < 0.05). Conclusion. Our depigmentation cream is a moderate effective agent, well tolerated and can be considered as an alternative treatment of melasma. Twice-daily application may enhance the efficacy of treatment instead of twice-weekly application in the maintenance period.