Objective: This systematic review and meta-analysis aimed to determine the benefits of an exercise intervention based on small-sided soccer games (SSSGs) on health-related physical fitness and cardiometabolic health in previously untrained children and adolescents. Methods: A systematic search on PubMed/MEDLINE, Web of Science, Scopus, Cochrane, and EBSCO databases was performed. Randomized or non-randomized controlled trials conducted in previously untrained children or adolescents (age < 18 years) that assessed the effect of SSSG-based intervention on health-related physical fitness and cardiometabolic risk biomarkers were included. Primary outcomes were cardiorespiratory fitness and waist circumference. Evidence was synthesized as the mean difference or standardized mean difference using a random-effects meta-analysis. The quality of evidence was assessed using ROB2 and ROBINS-I tools. Results: Sixteen studies (n = 2872 participants) were included in this meta-analysis. SSSGs significantly improved cardiorespiratory fitness (SMD, 0.12 [0.01; 0.23]) and showed a non-significant trend in decreased waist circumference (-7.49 cm [-15.03; 0.06]). Additionally, SSSGs significantly decreased systolic (MD, -3.85 mmHg [-5.75; -1.94]) and diastolic blood pressure (MD, -1.26 mmHg [-2.44; -0.08]) and triglycerides (-30.34 mg<middle dot>dL-1 [-45.99; -14.69]). No effects on body composition or other cardiometabolic risk biomarkers were observed. After a sensitivity analysis, waist circumference and muscle strength were also shown to improve significantly following SSSGs. Comparisons between SSSG and other types of exercise interventions showed no differences in improved physical fitness or cardiometabolic risk. Conclusions: SSSG-based interventions effectively improve cardiorespiratory fitness, blood pressure, triglycerides, muscle strength, and waist circumference. There is less evidence of the effects of SSSGs on other health markers. Particular attention should be given to improving SSSG protocol reporting in future studies.