PCOS is one of the most prevalent endocrine disorders among women of reproductive age, often involving obesity, insulin resistance, and mental health challenges that reduce health-related quality of life (HRQOL). Although metformin has been shown to improve HRQOL in PCOS patients, it is unclear whether this effect is due to the drug itself or its metabolic benefits. This study included 66 PCOS patients from the University Medical Center Mainz, in two groups: 31 received metformin (M-group) and 35 received alternative or no treatment (C-group). HRQOL and distress were assessed at baseline and after 6 months using the Modified PCOS-Questionnaire (MPCOSQ) and the Hospital Anxiety and Depression Scale (HADS). At baseline, the M-group had significantly worse metabolic markers, including HOMA-IR, waist circumference, Visceral Adiposity Index, and Fatty Liver Index. By follow-up, this group showed greater improvements in these markers. However, both groups improved similarly in HRQOL and distress. Regression analysis revealed that improvements in HOMA-IR and BMI were associated with better HRQOL scores. Group assignment was not a significant predictor. These findings may indicate that improvements in HRQOL and reduced distress are linked to metabolic changes associated with metformin use, underscoring the potential relevance of addressing metabolic health in treatment approaches.