Postinflammatory hyperpigmentation (PIH) is a common acquired hyperpigmentation disorder that can cause significant psychosocial impacts. Cysteamine has been shown to be an effective depigmenting agent for hyperpigmentation disorders, and a clinical trial was conducted to assess the efficacy and safety of cysteamine-isobionicamide complex for treating PIH. Forty patients were randomized into treatment and control groups, with assessments collected at baseline, week 4, 8, and 16. The treatment group showed significant improvement in dermatological assessments, MASI score, TPHI score, and life quality score compared to the control group. Mexameter® and VISIA skin analysis also showed significant improvement in the melanin index and erythema index score at week 16, with cellular resolution OCT imaging revealing decreased melanosome capping and fewer hyper-reflective melanophages. This study suggests that the cysteamine-isobionicamide complex has the potential to be a viable treatment option for PIH.