Background Polycystic ovarian syndrome (PCOS) is a complex endocrine disorder that affects reproductive and metabolic health in women, often leading to challenges with fertility, insulin resistance, and cardiovascular risk. Melatonin, Vitamin D, and metformin are known to address specific aspects of PCOS, but their combined effects on both reproductive anatomy and metabolic markers remain to be fully understood. This study examines the impacts of these agents on ovarian and uterine histology and hematological profiles in women with PCOS. Method A prospective interventional study was conducted at Jinnah Medical College, Peshawar, involving 101 women diagnosed with PCOS. Participants were divided into three groups, each receiving one of the following treatments: melatonin, Vitamin D, or metformin. A stereological analysis was used to evaluate ovarian and uterine tissue changes, while hematological profiles were assessed through blood sample analysis. Statistical comparisons were conducted with a significance level set at p < 0.05. Results Conclusion Keywords Vitamin D was associated with significant improvements in ovarian volume and follicular density, indicating enhanced ovarian structure and potential benefits for fertility. The metformin group demonstrated notable reductions in LDL and total cholesterol levels, supporting its role in improving lipid profiles and addressing cardiovascular risks in PCOS. Melatonin showed moderate effects on ovarian and hematological parameters, suggesting a supportive rather than primary role. The study supports the use of Vitamin D for improving ovarian morphology and follicle development, while metformin addresses metabolic concerns by enhancing lipid profiles. Together, these findings highlight the potential of a combined therapeutic approach for PCOS, addressing both reproductive and metabolic challenges. Future research should explore the effects of these treatments in combination and evaluate long-term outcomes.