Background <p>The continuing rise in overweight and obesity among children and adolescents portends a life-course public-health crisis. Although evidence has been accumulating that exercise interventions improve health in those with overweight or obesity, few studies have integrated multidimensional health outcomes within a unified analytical framework. To systematically evaluate the effects of exercise interventions on multidimensional health outcomes—including anthropometric, cardiometabolic, cardiorespiratory, and mental health indicators—among children and adolescents with overweight or obesity, and to explore implications for global obesity prevention and control.</p> Methods <p>Six databases (PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang Data) were searched from inception to January 10, 2025, for randomized controlled trials of exercise interventions in children and adolescents with overweight or obesity. Data were pooled using random- or fixed-effects models, as appropriate. Risk of bias was assessed using the Cochrane Risk of Bias Tool (RoB 2.0), and the certainty of evidence was rated with the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. The protocol was registered with PROSPERO (CRD420251169879).</p> Results <p>A total of 176 trials (11,696 participants from 32 countries) were analyzed. Exercise interventions significantly reduced body mass index (MD: −1.25&#xa0;kg m⁻², 95% CI: −1.51 to −0.98), waist circumference (MD: −2.86&#xa0;cm, 95% CI: −3.52 to −2.20), and body fat percentage (MD: −2.39, 95% CI: −2.81 to −1.96); improved cardiorespiratory fitness (maximal oxygen consumption MD: 2.83 mL kg⁻¹ min⁻¹, 95% CI: 2.17 to 3.50; peak oxygen uptake MD: 2.56 mL kg⁻¹ min⁻¹, 95% CI: 1.86 to 3.27); and lowered resting heart rate (MD: −2.89&#xa0;bpm, 95% CI: −3.82 to −1.97). Cardiometabolic indicators also improved, with reductions in systolic blood pressure (MD: −3.90 mmHg, 95% CI: −5.34 to −2.46) and diastolic blood pressure (MD: −1.70 mmHg, 95% CI: −2.68 to −0.71); total cholesterol (MD: −0.35 mmol/l, 95% CI: −0.43 to −0.27), triglycerides (MD: −0.23 mmol/l, 95% CI: −0.28 to −0.17), and low-density lipoprotein cholesterol (MD: −0.28 mmol/l, 95% CI: −0.35 to −0.20) decreased, accompanied by an increase in high-density lipoprotein cholesterol (MD: 0.08 mmol/l, 95% CI: 0.05 to 0.10). Fasting glucose (MD: −0.20 mmol/l, 95% CI: −0.26 to −0.13) and fasting insulin (MD: −3.93 µU/mL, 95% CI: −4.80 to −3.06) also declined. Regarding mental health, exercise improved self-esteem (SMD: 0.18, 95% CI: 0.04 to 0.33) and self-worth (SMD: 0.25, 95% CI: 0.10 to 0.39), although the evidence for effects on depression and anxiety was limited. The observed effects varied across prespecified subgroups defined by exercise dose and type, region, country income level, sex, and obesity or metabolic phenotypes.</p> Conclusions <p>Exercise interventions consistently improved multidimensional health outcomes in children and adolescents with overweight or obesity, showing dose- and type-dependent effects with greater benefits in higher-risk groups. These findings underscore the value of exercise as a key strategy to address obesity, while recognizing that political and economic barriers may hinder policy translation. Future research should refine intervention approaches and strengthen pathways from evidence to policy implementation.</p>