Objective: To investigate the clinical efficacy and safety of 308-nm excimer light combined with paeonol ointment in the treatment of female neurodermatitis, and to provide evidence for optimizing therapeutic strategies for neurodermatitis. Methods: A total of 200 female patients with neurodermatitis treated between January 2021 and January 2024 were enrolled and randomly divided into a control group and a combination group, with 100 cases in each group. The control group received 308-nm excimer light therapy, while the combination group received additional topical application of paeonol ointment on the basis of excimer light therapy. Both groups were treated continuously for 3–5 weeks. Changes in Eczema Area and Severity Index (EASI), Numerical Rating Scale (NRS) for pruritus, and Dermatology Life Quality Index (DLQI) scores before and after treatment were compared between the two groups. Adverse reactions during treatment were also recorded and analyzed. Results: After treatment, EASI, NRS, and DLQI scores in both groups were significantly lower than those before treatment, and the improvement in the combination group was significantly better than that in the control group (P＜0.05). No serious adverse reactions were observed in either group. There was no significant difference in the incidence of mild local adverse reactions such as erythema and burning sensation between the two groups (P＞0.05). Conclusion: The combination of 308-nm excimer light and paeonol ointment is effective and safe in the treatment of female neurodermatitis. It can effectively reduce skin lesion severity, relieve pruritus, and improve patients’ quality of life, and is worthy of clinical promotion.