Background This systematic review aims to evaluate the effects of exercise combined with diet (ECWD), exercise alone, diet alone, and no intervention on body composition and serum biochemical markers in adolescents with obesity to provide reference for solving the metabolic disorders of adolescents caused by obesity. Contents Studies published before January 5, 2021 were retrieved from PubMed, Web of Science, Ovid, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang data, VIP database, and SinoMed. Randomized controlled trials with an age between 10 and 20 years, body mass index (BMI) ≥28 kg/m 2 or ≥95th percentiles, no history of endocrine and metabolic diseases, heart disease, hematologic disease, and so on before the trial were included. Summary Fifteen of the 50,155 studies met the criteria. Meta-analysis showed that ECWD was more effective in reducing BMI (kg/m 2 ) (−2.45 kg/m 2 , 95% CI: −3.06; −1.85) and fat thickness of back (−13.77 mm, 95% CI: −15.92; −11.62), abdomen (−11.56 mm, 95% CI: −14.04; −9.09), and upper arm (−14.81 mm, 95% CI: −16.74; −12.89) than other interventions; in reducing body fat (−7.03 kg, 95% CI: −9.77; −4.29) and thigh circumference (−4.05 cm, 95% CI: −5.58; −2.52), ECWD and diet alone were more effective than exercise alone; ECWD and exercise alone were more effective in reducing waist circumference (−6.05 cm, 95% CI: −8.37; −3.72), waist-to-hip ratio (WHR; −0.06, 95% CI: −0.11; −0.01), upper arm circumference (−2.57 cm, 95% CI: −3.70; −1.45), triglycerides (TG; −0.30 mmol/L, 95% CI: −0.45; −0.14), total cholesterol (TC; −0.30 mmol/L, 95% CI: −0.59; −0.01), and low density lipoprotein (LDL; −0.22 mmol/L, 95% CI: −0.40; −0.04) than diet alone. ECWD also had effects on tumor necrosis factor-α (TNF-α), interleukin-6, leptin, and so on. Outlook ECWD is more effective than exercise alone, diet alone, or no intervention in solving the problems of body shape and metabolic disorder of adolescents with obesity.