Emerging lifestyle changes due to rapid urbanization have led to an epidemiological transition and the rising prevalence of obesity is responsible for major non-communicable diseases (NCDs) which have further aggravated due to the COVID-19 pandemic. This study aims to assess the effectiveness of a comprehensive school-based intervention on diet and physical activity-related behavior of adolescents. In 2019, a cluster-randomized controlled trial was conducted in randomly selected (n=8) private schools. A 2-year intervention program was implemented over consecutive academic years (2019-2020 and 2020-2021) with students who were in the 6th and 7th grades when the study began. Four schools were randomly assigned to the intervention (n=794) and four schools to the control group (n=774). The difference in changes in diet and physical-activity-related behaviors of the students between the intervention and control schools were not significant in the intention to treat analysis probably due to the large drop-out due to COVID-19 measures: 304 students were available for follow-up in the intervention group and 122 in the control group (391 cases were excluded to make data comparable with baseline survey). The intake of vegetables (once a day) [β=0.35, OR=1.42, 95% CI (1.03, 1.95)] in the per-protocol analysis has increased among adolescents in the intervention group as compared to the control group. The findings of this study indicated a positive effect of the intervention on diet and physical-activity-related changes in the expected direction and highlights the importance of addressing such behavior to prevent obesity among adolescents and thus NCDs in the later stage of life.