BACKGROUND: Neglected tropical diseases (NTDs) are a group of communicable diseases affecting the poorest populations around the world. OBJECTIVE: To assess the effectiveness of interventions, including mass drug administration (MDA), water, sanitation, and hygiene (WASH), vector control, health education, and micronutrients supplementation, for NTDs among children and adolescents. METHODS: We conducted a literature search on the Cochrane Controlled Trials Register, Medline, and other databases until December 2020. We included randomized controlled trials and quasi-experimental studies conducted among children and adolescents. Two authors independently screened studies for relevance. Two authors independently extracted data, assessed the risk of bias, performed metaanalysis, and rated the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation. RESULTS: We included 155 studies (231 articles) involving 262 299 participants. For soil-transmitted helminthiasis, MDA may reduce the prevalence of Ascaris, Trichuris, and hookworm by 58%, 36%, and 57%, respectively.We are uncertain of the effect of health education,WASH, and iron supplementation on soil-transmitted helminthiasis prevalence. For Schistosomiasis, health education probably reduces the intensity and prevalence of S. mansoni, whereas micronutrient supplementation may reduce anemia prevalence and the infection intensity of S. hematobium compared with no supplementation.We are uncertain of the effect of MDA and vector control on Schistosomiasis outcomes. For trachoma, health education probably reduces the prevalence of active Trachoma, whereas we are uncertain of the effect of MDA,WASH, and vector control on Trachoma outcomes. There is limited data on the effectiveness of interventions for NTDs targeting children and adolescents. CONCLUSION: Future studies are needed to evaluate the relative effectiveness and cost-effectiveness of various interventions specifically targeting children and adolescents.