Background: Menopause, characterized by cessation of menstruation, is accompanied by various physiological and psychological changes. This randomized controlled trial (RCT) investigated the efficacy of a multi-domain lifestyle modification program in alleviating menopausal symptoms and promoting health behaviors among postmenopausal women residing in urban slums of Hyderabad, India. Methods: Eighty-two women aged 45–60 years experiencing menopausal symptoms were recruited. Participants were randomly assigned to either a 45-day lifestyle intervention group or a control group receiving standard care. The intervention program addressed six domains: health responsibility, physical activity, nutrition, spiritual growth, interpersonal relations, and stress management. The menopause rating scale (MRS) and a modified health-promoting lifestyle II (HPBII) questionnaire assessed menopausal symptoms and health behaviors at baseline and during follow-up. Results: The intervention group showed significant improvements (P < 0.05) in terms of overall HPBII scores compared to baseline, with the most notable changes observed in health responsibility, nutrition, and stress management domains. In addition, MRS scores indicating menopausal symptoms were significantly lowered (P < 0.05) in the intervention group. No significant changes were found in the control group in either health behaviors or menopausal symptoms. After the intervention, the experimental group showed a significant improvement in HPBII scores compared to the control group, particularly in health responsibility, nutrition, interpersonal relationships, and stress management sub-domains. Conclusion: This RCT suggested that a comprehensive lifestyle modification program could effectively improve health behaviors and alleviate menopausal symptoms in postmenopausal women residing in under-resourced settings. Further research is warranted to explore the program’s long-term sustainability and generalizability.