Background Polycystic ovarian syndrome (PCOS) is a prevalent endocrine disorder among reproductive aged women, characterized by hormonal dysregulation, metabolic abnormalities, and structural ovarian changes. Conventional treatments, including clomiphene citrate, often have variable efficacy, particularly in ovulation induction. Melatonin, recognized for its antioxidant and anti inflammatory properties, has shown potential as an adjunct therapy in managing PCOS due to its positive effects on ovarian and uterine health. This study aims to evaluate the effects of melatonin and clomiphene citrate, both individually and in combination, on hormonal, metabolic, and histopathological outcomes in women with PCOS. Methodology This ‘randomized controlled trial’, conducted at ‘Jinnah Medical College’ from January 2022 to January 2023, involved 120 women diagnosed with PCOS. ‘Participants were assigned to three groups: Group A received melatonin therapy’, Group B received clomiphene citrate, and Group C received a combination of both. Key outcome measures included hormonal levels (LH, FSH, testosterone, and AMH), metabolic parameters (HOMA-IR, HDL, and triglycerides), and histopathological assessments (follicle count, follicular size, and endometrial thickness). Data were analyzed using ANOVA ‘and Chi-square tests, with significance set at p < 0.05’. Results The combination therapy group showed the most significant improvements in ovulation and pregnancy rates (75% and 35%, respectively, p < 0.05). Combination therapy also yielded favourable hormonal and metabolic profiles, with lower serum testosterone, improved LH/FSH ratios, and better HOMA-IR and lipid levels. Histopathological outcomes, including follicular Conclusion size, count, and endometrial thickness, were more pronounced in the combination group, supporting enhanced ovarian function and uterine receptivity. The findings suggest that combining melatonin with clomiphene citrate may optimize treatment outcomes in women with PCOS, particularly in those unresponsive to clomiphene citrate alone. This combined approach improves both biochemical and structural ovarian characteristics and shows promise as a safer, more effective PCOS management strategy.