Summary Background  Some probiotics can ameliorate childhood atopic dermatitis (AD). Prebiotics have also shown some efficacy, although when combined with probiotics as synbiotics, their efficacy may improve. Objective  We compared the effects of Lactobacillus salivarius and fructo‐oligosaccharide (synbiotic) with fructo‐oligosaccharide alone (prebiotic) on children with moderate to severe AD. Methods  We randomly assigned 60 children aged 2–14 years with moderate to severe AD SCORing AD (SCORAD) > 25 to a treatment (synbiotic) or a control (prebiotic) group (30 per group). They received one capsule twice daily for 8 weeks containing either L. salivarius plus fructo‐oligosaccharide (treatment) or fructo‐oligosaccharide only (control). SCORAD indices were monitored at weeks 0, 4, 8 and 10 (post‐treatment). Laboratory results and AD medication use were also monitored. Results  Baseline demographic and clinical characteristics and SCORAD scores were similar between the two groups. At 8 weeks, the treatment group SCORAD scores (27·4 ± 12·7) were significantly lower than for the controls (36·3 ± 14·9) (P = 0·022); this difference remained at 10 weeks. At 8 weeks, treatment group AD intensity was significantly lower (P = 0·013); more children had mild AD in the treatment group (52%; 14/27) than the control group (30%; 8/27) (P = 0·024). Medication use frequency and eosinophil cationic protein levels were significantly reduced in the treatment group at 8 weeks compared with 4 weeks. Conclusion  A synbiotic combination of L. salivarius plus fructo‐oligosaccharide is superior to the prebiotic alone for treating moderate to severe childhood AD. However, continued follow‐up will be necessary to ascertain long‐term benefits.