Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by reproductive, metabolic, and hormonal dysregulation. Emerging evidence suggests leptin, an adipocyte-derived hormone, plays a key role in linking obesity, insulin resistance, and reproductive dysfunction in PCOS. Objective: To evaluate the interplay of leptin with metabolic and hormonal biomarkers in women with PCOS and its potential role as a mediator of pathophysiological abnormalities. Methods: A case–control study was conducted on 100 women aged 20–40 years, comprising 50 PCOS patients (diagnosed by Rotterdam criteria) and 50 healthy controls. Clinical parameters, anthropometry, and biochemical markers—including leptin, LH, FSH, testosterone, fasting insulin, fasting glucose, and HOMA-IR—were assessed. Statistical comparisons and correlation analyses were performed, with significance set at p<0.05. Results: Women with PCOS had significantly higher BMI, acne, hirsutism, amenorrhea, and ultrasonographic evidence of polycystic ovaries compared with controls (p<0.001). Serum leptin levels were markedly elevated in PCOS (32.70±5.19 vs. 21.42±2.79 ng/mL, p<0.0001). PCOS women also showed increased LH, LH/FSH ratio, testosterone, fasting insulin, fasting glucose, and HOMA-IR (p<0.0001 for all). Correlation analysis demonstrated strong positive associations of leptin with BMI, LH, testosterone, LH/FSH ratio, fasting insulin, fasting glucose, and HOMA-IR, whereas age showed a weak negative correlation. Conclusion: Elevated leptin levels and their significant correlations with insulin resistance, hyperandrogenism, and gonadotropin imbalance highlight leptin’s role as a metabolic mediator in PCOS. These findings reinforce the need for integrating metabolic and hormonal profiling in PCOS evaluation and suggest leptin as a potential biomarker and therapeutic target.