Present evidence regarding the efficacy and safety of levamisole in childhood nephrotic syndrome (NS), particularly the steroid-sensitive NS (SSNS), is limited. We searched relevant databases such as PubMed/MEDLINE, Embase, Google Scholar, and Cochrane CENTRAL till June 30, 2020. We included 12 studies for evidence synthesis (5 were clinical trials that included 326 children). The proportion of children without relapses at 6–12 months was higher in the levamisole group as compared to steroids (relative risk [RR]: 5.9 [95% Confidence interval (CI): 0.13–264.8], I2 = 85%). Levamisole as compared to the control increased the proportion of children without relapses at 6–12 months (RR: 3.55 [95% CI: 2.19–5.75], I2 = 0%). The GRADE evidence was of “very-low certainty” except for the comparison of levamisole with control, the latter being of “moderate certainty.” To conclude, levamisole given to children with SSNS is beneficial in preventing relapses and achieving remission as compared to placebo or low-dose steroids. Good-quality trials are needed to provide a robust evidence in this regard. PROSPERO Registration number: CRD42018086247.