Background: Rising rates of overweight and obesity among adolescents pose serious long-term physical and psychological health risks. Nurse-led interventions are considered effective strategies for promoting healthy lifestyles and preventing obesity. Aim: This study aimed to evaluate the effectiveness of nurse-led interventions in preventing childhood and adolescent overweight and obesity. Subjects and Method: Design: A quasi-experimental one-group pre-, post-, and follow-up design was utilized. Setting: The study was conducted in five districts of Port Said City, each with one governmental secondary school for girls. A purposive sample of 112 adolescent girls aged 15–18 years with BMI above the 85th percentile was recruited in two randomly selected governmental secondary schools. Data were collected using five tools: (I) Physical Activity Level Questionnaire, (II) Food Frequency Questionnaire, (III) Screen Time Assessment, (IV) Waist Circumference Percentile Charts, and (V) BMI-for-age percentiles. Results: significant improvements were observed in physical activity, dietary habits, and screen time behaviors (p < 0.001). healthy dietary habits increased from 19.6% pre-program to 41.1% post-program, while high physical activity rose from 29.5% to 37.5%, and healthy screen time (<2 hours/day) increased from 17.9% to 42.9%. Normal waist circumference improved from 47.3% to 58.0%, and normal BMI increased from 0% to 42.9%, with reductions in overweight and obesity. Conclusion: the nurse-led intervention program was effective in preventing overweight and obesity among adolescent girls. Recommendations: Nurse-led lifestyle programs should be integrated into community health services with regular follow-up, strengthened parental involvement, and expanded implementation on a larger scale to enhance adolescent obesity prevention