Background The prevalence of obesity among children as well as the beneficial effects of physical exercise (PE) on weight loss has been determined by modulating the secretory factors of adipose tissue. PE has also been shown to have beneficial effects on obesity. Objective The objective of this systematic review and meta-analysis was to investigate the effects of physical exercise (PE) on adiponectin and other important health markers in children. Data sources We searched 6 electronic databases (PubMed/Medline, Embase, Cochrane Library, Cinahl, Scopus, and Web of Science) and Google Scholar for randomized controlled trials from inception to December 15, 2021. We used random-effects models to estimate weighted mean difference (WMD) with 95% confidence intervals (CI). Study selection Fourteen studies were included (N = 468 participants; mean age: 14 years). Results In general, PE increased adiponectin (WMD: 0.91 mu g/mL; 95% CI, 0.27 to 1.55, p = 0.005), high-density lipoprotein cholesterol (HDL-C) (WMD: 1.01 mg/dL; 95% CI, 0.33 to 1.69, p = 0.004), and VO(2)max (WMD: 2.52 mL.kg.min; 95% CI, 1.41 to 3.62, p = 0.00,001). The levels of c-reactive protein (WMD: -0.37 mg/L; 95% CI, -0.57 to -0.17, p = 0.0003), insulin (WMD: -4.61 mu IU/ml; 95% CI, -5.46 to -3.76, p = 0.00,001), fasting glucose (WMD: -5.11 mg/dL; 95% CI, -7.88 to -2.34, p = 0.0003), and insulin resistance index (WMD: -1.44; 95% CI, -1.92 to -0.96, p = 0.00,001), decreased significantly. Conclusion Our study showed that PE may increase the level of adiponectin, HDL-C, and VO(2)max in children.