ObjectiveTo evaluate the efficacy and adverse effects of phosphodiesterase 4 inhibitors in children with mild-to-moderate atopic dermatitis.MethodsElectronic searches were conducted based on PubMed, Cochrane Library, EMBASE, and Web of Science using Medical Subject Headings terms and relevant keywords. Using response rates as the primary outcome and adverse effects as the secondary outcome, statistical analysis was performed via Stata 15.1 SE, with Cochrane Q and statistics used for heterogeneity assessment. Publication bias and sensitivity analyses were conducted using various methods. Risk of bias was assessed using the Cochrane risk of bias tool.ResultsThe analysis included six randomized controlled trials involving 4681 children with atopic dermatitis. Phosphodiesterase 4 inhibitors were associated with significantly higher response rates than vehicle controls (odds ratio = 2.01, 95% confidence interval: 1.58 to 2.56, p < 0.001,  = 54.8%), with no significant difference in adverse effect incidence (odds ratio = 1.07, 95% confidence interval: 0.87 to 1.30, p = 0.536,  = 11.8%). Subgroup analysis revealed varying response rates among different phosphodiesterase 4 inhibitors, with crisaborole showing the least adverse effects.ConclusionOur meta-analysis revealed that children with atopic dermatitis treated with phosphodiesterase 4 inhibitors experienced higher remission rates and comparable adverse effect rates compared with vehicle controls. Currently, crisaborole appears to be the optimal choice for balancing safety and efficacy. As research in this area is still in its early stages, further high-quality trials are essential for establishing standards of clinical care.INPLASY registration number: INPLASY202520121.