This study explores an adolescent ambassador program that promotes substance abuse awareness in rural villages, and studies its effects on self-esteem, peer influence, and family communication. This school-based intervention was part of a larger program that mentored adolescent youth as change agents to promote health and social awareness in rural communities in India, in alignment with UN Sustainable Development Goal 3 (good health and wellbeing). One hundred and forty-three ambassadors between 8 and 18 years of age, representing rural communities in 23 economically challenged villages across 11 states of India, participated in the study. Adolescents were mentored to implement substance abuse awareness programs among their peers and the village community. During the training, the ambassadors used a variety of didactic, creative, and technological modalities. Pre- and post-analyses assessed ambassadors’ self-esteem, personal substance use, perceptions of peer substance abuse, comfort with discussing substance abuse, and perceptions of social support. Ambassadors’ self-esteem increased significantly. In addition, positive changes related to the perception of parents’ and friends’ attention, as well as comfort in addressing substance abuse topics with others, were observed.