There are limited data on successful weight management approaches among adolescents from underserved communities. The primary aim of this study was to obtain preliminary data on the efficacy, safety, and acceptability of a lifestyle intervention with milk-based supplements among adolescents from underserved communities. The secondary aims of this study were to assess change in adiposity indices and metabolic indices and to measure compliance. The authors conducted a 12-week open-labeled lifestyle intervention. Adolescents were taught a structured meal plan, including the use of 2 milk-based supplements daily, and participated in weekly lifestyle counseling. Overweight was defined as a body mass index >85th percentile. Percent total body fat was estimated using bioelectric impedance. Fasting blood samples were used to measure insulin indices and other biochemical safety tests. The sample consisted of 40 adolescents (70% girls, 83% minority). Although there was no significant change in body mass index (median [Q1, Q3]; -0.10 [-0.91, 0.61] kg/m(2), P = .26), participants showed a decrease in body mass index z score (-0.03 [-0.08, 0.01] SD, P = .01]), weight z score (-0.04 [-0.11, 0.02] SD, P = .001), and percent total body fat (-1.20 [-2.55, -0.12]%, P = .0001). No new onset of type 2 diabetes mellitus was reported, and plasma vitamin D increased (P < .01). Consumption of milk-based drinks increased from a median of 4.5 to 13.5 servings per week, whereas sugary beverages decreased from 8.0 to 3.8 servings per week. A lifestyle intervention that includes milk-based supplements may safely improve some adiposity indices and decrease intake of sugary beverages among overweight adolescents from underserved areas.