ImportanceMental health stigma is a considerable barrier to help-seeking among young people. ObjectiveTo systematically review and meta-analyze randomized clinical trials (RCTs) of interventions aimed at reducing mental health stigma in young people. Data SourcesComprehensive searches were conducted in the CENTRAL, CINAHL, Embase, PubMed, and PsycINFO databases from inception to February 27, 2024. Search terms included "stigma," "mental health," "mental disorders," "adolescents," "youth," and "randomized controlled trial." Study SelectionInclusion criteria encompassed RCTs involving interventions aimed at reducing mental health stigma among young people (aged 10-24 years). Studies had to report outcomes related to stigma or help-seeking behaviors. Exclusion criteria included grey literature and studies without results. Data Extraction and SynthesisData were extracted independently by 7 authors (M.A.C., D.N., F.B., S.C., & Aacute;.I.L., J.C., V.M.) using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Risk of bias was assessed with the Cochrane risk-of-bias tool. Three-level multivariate meta-analyses were conducted to account for within-study correlations and to maximize data use. Standardized mean differences (SMDs) (Hedges g) and odds ratios (ORs) with 95% CIs were calculated. The data analysis was conducted from May 30 through July 4, 2024. Main Outcomes and MeasuresPrimary outcomes included stigma-related knowledge, attitudes, behaviors, and general stigma. Help-seeking outcomes were categorized into attitudes, intentions, and behaviors. Secondary outcomes included self-efficacy and empowerment. ResultsA total of 97 studies were included in the systematic review, representing 43 852 young people (mean [IQR] age, 18.7 [15.8-21.3] years; mean [IQR] females, 59.2% [49.4%-72.0%]), and 74 studies were included in 3-level multivariate meta-analyses. Significant short-term effect sizes were found for stigma-related knowledge (SMD, 0.66; 95% CI, 0.43-0.89), attitudes (SMD, 0.38; 95% CI, 0.20-0.56), behaviors (SMD, 0.29; 95% CI, 0.13-0.45), and general stigma (SMD, 0.20; 95% CI, 0.06-0.34) and for help-seeking attitudes (SMD, 0.18; 95% CI, 0.09-0.28) and intentions (SMD, 0.14; 95% CI, 0.07-0.21). Social contact interventions had a greater influence on stigma-related behaviors than did educational approaches. Conclusions and RelevanceThese findings suggest that interventions to reduce mental health stigma among youth are beneficial in the short term. Further high-quality RCTs with long-term follow-up are needed to better understand and enhance these interventions' outcomes.