This study evaluates the efficacy and safety of soothing moisturizing repairing cream combined with desonide in the treatment of atopic dermatitis (AD) in children in the real world. A total of 37 children with AD were randomly divided into experimental (17) and control (20) groups. For the experimental group, treated with moisturizing cream combined with desonide cream, the maintenance period was with moisturizer alone. For the control group, treated solely with desonide, the maintenance period was with nothing. Clinical assessments were made before and 1, 2, and 4 weeks after treatment. Efficacy indicators are compared between the 2 groups, and the relieving effect of moisturizer on the maintenance period of AD in children is observed. Adverse reactions are also recorded. After 4 weeks of treatment, the cure rate and effectiveness rate in the experimental group were 52.9% and 100%, respectively, compared to 0% and 60% in the control group; the estimated median maintenance time was 48 days for the control group and 73 days for the experimental group. The incidence of adverse reactions shows no statistical significance. The combination of moisturizing cream and desonide in the treatment of AD in children is highly effective and safe. It is worth promoting for clinical application due to its significant therapeutic effects and high safety profile.