Post-acne hyperpigmentation (PAH) occurs secondary to acne vulgaris and may cause significant adverse effects. Although may occur in any skin types, PAH has been found to be more common and severe in people with colored skin. This study aimed to assess the effectiveness of combination serum containing galactomyces ferment filtrate (GFF), dexpanthenol, and Centella asiatica for treating PAH. This randomized controlled clinical trial involved Fitzpatrick skin type (FST) IV and V patients with PAH. Subjects were equally divided into treatment group, who received three drops of combination serum twice daily for 8 weeks, and placebo group. The melanin index (MI) and Lightness (L*) score were assessed every 2 weeks. Out of 51 subjects, the L* score of the treatment group in subjects with FST V was significantly higher on the 4th and 6th week compared to the placebo group (P ˂ 0.05). The MI of subjects with FST IV was significantly lower compared to the placebo group after 8 weeks (P ˂ 0.05). The treatment group showed consistent increasing and decreasing trend in L* score and MI, respectively (r ˃ 0.9, P ˂ 0.05). Combination serum containing GFF, dexpanthenol, and C. asiatica may be effective in treating PAH in subjects with colored skin by accelerating lessening of PAH.