A remarkable change in growth and development occurs during the adolescence. Changes occur in their capability to understand, judge and appraise situations and informations. School plays an important role in this transition period from childhood to adulthood. Comprehensive interventions provided at school promote physical and psychological well-being. Thus the present study was aimed at assessing the effectiveness of comprehensive intervention package on psychological and bio-physiological parameters among adolescents. Quantitative experimental pre-test and post test control group design was used. Comprehensive intervention package aimed at promoting assertive communication, reducing stress, enhancing coping, peer relationship and self-esteem was found to be more effective on the experimental group compared to the control group with no treatment. © 2016, Indian Journal of Public Health Research and Development. All rights reserved.