To systematically review and synthesize the safety and efficacy of coronavirus disease-2019 (COVID-19) vaccines in children and adolescents. PubMed, EMBASE, Web of Science, Cochrane Library databases, the International Clinical Trials Registry Platform (ICTRP), the Chinese Clinical Trials Registry (ChiCTR), and ClinicalTrials.gov website were searched to collect accessible randomized controlled trials (RCTs) about the safety and efficacy of human COVID-19 vaccines in children and adolescents until May 1, 2022. Three steps, including duplicate removal, title and abstract screening, and full-text review, were used to screen the studies. The Cochrane risk-of-bias tool for RCTs was used to assess the bias risk of the included studies. Microsoft Excel 16.57 (2021) software was used for data extraction and analysis. (PROSPERO Code No: CRD42021295422). COVID-19 vaccines were evaluated in a total of 10 950 children and adolescents in seven published studies and over 49 530 participants in 26 ongoing randomized controlled trials. Descriptive findings of the included published studies were reported stratified by vaccine type. The overall, local, and systemic adverse events following immunization (AEFIs) reported in most trials were similar between the vaccine and placebo groups. Most of the reactions reported were mild to moderate, whereas a few were severe. The common adverse events were injection-site pain, fever, headache, cough, fatigue, and muscle pain. Few clinical trials reported serious adverse events, but most of them were unrelated to vaccination. In terms of efficacy, the investigated messenger RNA (mRNA) vaccine was found to be 90.7%-100% efficacious in preventing COVID-19 among children and adolescents, revealing good efficacy profiles in this age group. Among children and adolescents, the safety of current COVID-19 vaccines is acceptable, and studies have suggested that mRNA vaccines can provide high protection against COVID-19 infection in pediatric age groups.