Objective To analyze the clinical efficacy and safety of prednisone acetate combined with medical wound care solution for skin allergies. Methods A total of 126 patients with skin allergies treated at our dermatology department from March to July 2026 were randomly divided into an observation group and a control group (63 cases each). The control group received oral prednisone acetate alone, while the observation group additionally received local wet compresses with medical wound care solution. Both groups were treated for 14 days. Outcomes included total clinical effectiveness, symptom resolution time, skin barrier function, anxiety scores (SAS), satisfaction, adverse events, and 3-month recurrence rate. Results The observation group showed higher total effectiveness (93.65% vs. 77.78%, P<0.05), shorter resolution times for erythema, itching, exudation, and swelling (P<0.05), the transepidermal water loss (TEWL) level in the observation group was lower than that in the control group, while the stratum corneum hydration content was higher than that in the control group (P<0.05). lower SAS scores and better satisfaction of the observation group(P<0.05), lower adverse event rate (6.35% vs. 19.05%, P<0.05), and lower 3-month recurrence rate (4.76% vs. 20.63%, P<0.05) than the control group. Conclusion Prednisone acetate combined with medical wound care solution can rapidly relieve symptoms, repair skin barrier, and reduce recurrence and adverse events, showing high clinical value.