Background and purpose: Obesity has become a serious public health problem and family-and school-based interventions including physical exercise and diet control have been widely applied to attempt to combat this issue. The purpose of our study was to verify the effectiveness of an obesity-related comprehensive intervention model aimed at improving quality of life (QoL) among adolescents. Methods: A cluster randomized controlled trial (RCT) was conducted involving 948 subjects who were divided into an intervention group (n = 518) and a control group (n = 430). The intervention group received 1 year of obesityrelated health education, physical exercise, and diet control. Their baseline body mass index (BMI) was calculated, and their QoL and basic information were assessed both before and after the intervention period using a selfdesigned Adolescent Quality of Life Scale and a basic information questionnaire. Results: After the intervention, significant differences in the psychological, social, and pubertal dimensions, and in total QoL (P < 0.05) were observed in the intervention group relative to the control group. Improved psychological QoL in the intervention group was our most robust study finding, with increases in psychological (B = 1.883, SE = 0.646, P = 0.004), pubertal (B = 0.853, SE = 0.296, P = 0.004) and total (B = 3.024, SE = 1.214, P = 0.013) QoL all being higher in this group. This intervention effect was found to be more substantial in boys than in girls. Conclusions: Family-individual-school-based interventions combining obesity-related health education, physical exercise, and diet control can improve psychological, pubertal, and total QoL in children, with these effects being most pronounced in boys. Trial registration: retrospectively registered NCT02343588.