Objective To explore the effect of ultra-picosecond laser combined with intense pulsed light therapy on skin lesions and skin status in patients with melasma. Methods A total of 80 patients with melasma treated in Nanjing Qixia Maisi Medical Beauty Clinic from August 2024 to April 2025 were selected, and they were divided into the control group and the observation group according to different treatment regimens, with 40 patients in each group. The control group was treated with intense pulsed light, and the observation group was treated with ultra-picosecond laser combined with intense pulsed light. The clinical efficacy, skin lesions, skin status and adverse reaction rate were compared between the two groups. Results The total effective rate of the observation group (95.00%) was higher than that of the control group (77.50%) (P <0.05). The scores of lesion area and color in the observation group after treatment were lower than those in the control group (P <0.05). The transepidermal water loss, epidermal sebum content and stratum corneum hydration in the observation group after treatment were better than those in the control group (P <0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P >0.05). Conclusion Ultra-picosecond laser combined with intense pulsed light can achieve definite therapeutic effect for patients with melasma. It is conducive to the improvement of skin lesions and skin status, without increasing the risk of adverse reactions, and presents high clinical safety.