To explore the effect of mupirocin combined with glucocorticoid in the treatment of patients with steroid-resistant atopic dermatitis/eczema. Methods A total of 65 patients with steroid-resistant atopic dermatitis/eczema admitted to Changzhou Dermatology Hospital from August 2020 to April 2021 were randomly divided into control group (n =32) and study group (n =33). The control group was treated with single glucocorticoid, and the study group was treated with mupirocin combined with glucocorticoid. The time required for relieving itching, the time of skin lesion regression, clinical efficacy and complications were compared between the two groups. Results The antipruritic time and skin lesion regression time of the study group were shorter than those of the control group, and the differences were statistically significant (P <0.05). The total effective rate of treatment in the study group was 96. 97%, which was higher than 81.25% in the control group, and the differences were statistically significant (P <0.05). The incidence of adverse reactions in the study group was 15.15%, which was higher than 12.50% in the control group, but the difference was not statistically significant (P >0.05). Conclusion The application of mupirocin combined with glucocorticoid in patients with steroid-resistant atopic dermatitis/ eczema has a good effect, which can effectively improve the clinical symptoms of patients, accelerate the regression of skin damage and itching, and help to improve the physical comfort of patients. Meanwhile, it can accelerate the rehabilitation process, and the incidence of adverse reactions is low , and the treatment safety is high.