Objective: This study aimed to evaluate serum adiponectin and leptin levels in women with polycystic ovary syndrome (PCOS) and assess their association with metabolic dysfunction, particularly insulin resistance, in a Pakistani population. Methods: A comparative cross-sectional study was conducted at Imran Idrees Teaching Hospital, Sialkot, from July 2024 to March 2025. A total of 150 women aged 18–35 years were enrolled, including 100 newly diagnosed PCOS patients (as per Rotterdam criteria) and 50 age-matched healthy controls. Anthropometric measurements (BMI, waist-to-hip ratio), fasting glucose, insulin, lipid profile, and serum adiponectin and leptin levels were recorded. HOMA-IR was calculated, and adiponectin/leptin ratio (A/L R) was used as a metabolic health indicator. Data were analysed using SPSS v26.0. Results: Women with PCOS had significantly higher BMI (29.1 ± 4.9 vs 23.8 ± 3.9 kg/m²; P < 0.001) and HOMA-IR (4.2 ± 1.5 vs 1.9 ± 0.6; P < 0.001) than controls. Serum adiponectin was significantly lower in PCOS (5.3 ± 1.9 µg/mL vs 9.1 ± 2.4 µg/mL; P < 0.001), while leptin was markedly higher (29.4 ± 9.5 ng/mL vs 15.8 ± 6.1 ng/mL; P < 0.001). The A/L R was reduced by over 75% in the PCOS group. Adiponectin showed strong inverse correlations with HOMA-IR and BMI, and remained an independent predictor of insulin resistance. Conclusion: Women with PCOS demonstrate significant adiponectin deficiency and leptin excess, indicative of metabolic dysfunction. The adiponectin/leptin ratio may serve as a valuable early marker for identifying insulin resistance and metabolic risk in PCOS.