Objective To explore the effect of oral isotretinoin combined with intense pulsed light on inffammatory lesions and hyperpigmentation improvement effect in patients with moderate to severe acne. Methods A total of 130 patients with moderate to severe acne who were treated in our hospital from January 2022 to January 2025 were selected, and they were divided into the control group and the observation group by the random number table method, with 65 patients in each group. The control group was treated with oral isotretinoin, and the observation group was treated with oral isotretinoin combined with intense pulsed light. The inffammatory lesion improvement effect, hyperpigmentation improvement effect, clinical efffcacy and adverse reaction rate were compared between the two groups. Results After treatment, the number of inffammatory lesions, GAGS score and PIH index in the two groups were lower than those before treatment, and those in the observation group were lower than those in the control group (P<0.05). The total effective rate of treatment in the observation group (92.31%) was higher than that in the control group (76.92%) (P<0.05). There was no statistically signiffcant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion Oral isotretinoin combined with intense pulsed light has an ideal clinical effect in patients with moderate to severe acne. It can effectively reduce the inffammatory response of moderate to severe acne, improve the PIH index, and has good overall tolerance, which is worthy of clinical application.