This longitudinal study with female youth in the slums of Kampala, Uganda (n = 130), explored the impact of the Transcendental Meditation® (TM®) technique on self-esteem, the primary outcome measure, and self-efficacy, gratitude, hope, tiredness, and resilience as secondary outcomes. Quality-of-life behaviors were also assessed, including excessive alcohol use. After baseline testing participants learned TM over five consecutive days. Participants practiced TM at home for 20 min twice a day and attended two follow-up sessions. Post-testing occurred at five months. Significant improvements in self-esteem (p < .001), self-efficacy (p < .001), gratitude (p < .001), and tiredness (p = .05) were found. A decrease in excessive alcohol use was also observed (p = .02). At eight months a short answer questionnaire showed improved physical health, decreased stress and anxiety levels, and improved relationships in the family and community. Our findings have important implications for enhancing the well-being and empowerment of these vulnerable female youth.