Objective To investigate the effect of gold microneedle radiofrequency combined with isotretinoin capsules on skin barrier function in patients with moderate to severe acne. Methods A total of 100 patients with moderate to severe acne treated at Suzhou Industrial Park Rodeo Medical Aesthetic Clinic from May 2023 to November 2025 were selected as the research subjects. According to different treatment plans, they were divided into group A and group B, with 50 patients in each group. Group A was treated with isotretinoin capsules, and group B was treated with gold microneedle radiofrequency combined with isotretinoin capsules. The clinical efficacy, skin lesion severity, skin barrier function and inflammatory factor levels were compared between the two groups. Results The total effective rate of group B (96.00%) was higher than that of group A (82.00%) (P<0.05). After treatment, the scores of lesion type, number and color in group B were lower than those in group A (P<0.05). After treatment, the sebum content and transepidermal water loss in group B were lower than those in group A, and stratum corneum hydration was higher than that in group A (P<0.05). After treatment, the levels of IL-4 and IL-6 in group B were lower than those in group A (P<0.05). Conclusion Gold microneedle radiofrequency combined with isotretinoin capsules is effective in the treatment of moderate to severe acne, which can effectively improve skin lesion severity and skin barrier function, and reduce inflammatory reactions.