Objective To analyze the effect of prednisone acetate combined with medical wound care solution on skin barrier function and symptom resolution time in patients with skin allergy. Methods A total of 126 patients with skin allergy admitted to the Department of Dermatology of our hospital from March to June 2026 were selected, and they were divided into the control group and the observation group by the random number table method, with 63 patients in each group. The control group received oral prednisone acetate alone, and the observation group was additionally treated with medical wound care solution on the basis of the control group. The clinical efficacy, symptom resolution time, skin barrier function, anxiety level [Self-rating Anxiety Scale (SAS) score], satisfaction, adverse event rate and recurrence rate were compared between the two groups. Results The total clinical effective rate of the observation group was 93.65%, which was higher than 77.78% of the control group (P<0.05). The resolution time of erythema, pruritus, exudation and swelling in the observation group was shorter than that in the control group (P<0.05). After treatment, the transepidermal water loss (TEWL) of the observation group was lower than that of the control group, and the stratum corneum hydration was higher than that of the control group (P <0.05). The SAS score of the observation group after treatment was lower than that of the control group, and the satisfaction was higher than that of the control group (P <0.05). The incidence of adverse events and the recurrence rate of the observation group were lower than those of the control group (P <0.05). Conclusion Prednisone acetate combined with medical wound care solution for the treatment of skin allergy can rapidly relieve clinical symptoms, repair skin barrier, reduce the risk of recurrence and adverse reactions, and has high clinical application value.