Background: Polycystic ovary syndrome (PCOS) is char- acterized by insulin resistance and hyperandrogenism, which contribute to increased production of reactive oxygen species (ROS) and reduced activity of antioxidant enzymes. Metform- in, a common drug in the treatment of PCOS, not only improves insulin sensitivity and corrects hormonal imbalances but may also reduce oxidative stress. The aim was to investigate the ef- fects of metformin on oxidative stress levels and antioxidant enzyme activity in the serum and follicular fluid of women with PCOS. Materials and Methods: Forty women with PCOS were ran- domly assigned to receive either metformin (1500 mg) or a pla- cebo (25 mg ORS solution) for 8 weeks, starting two months be- fore ovulation and continuing until oocyte retrieval. Serum and follicular fluid levels of malondialdehyde (MDA), total anti- oxidant capacity (TAC), and glutathione peroxidase/glutathione reductase (GPX/GRD) were measured using ELISA. Data were analyzed using the Independent T-Test, and the difference be- tween means was considered significant at the P<0.05 level. Results: The mean serum MDA levels (P=0.03) and follicu- lar fluid mean MDA levels (P=0.001) decreased significantly between the placebo and metformin groups. The mean serum TAC levels increased significantly between the placebo and metformin groups (P<0.001). There was no significant differ- ence in follicular fluid mean TAC levels between the placebo and metformin groups (P=0.276). There was no significant dif- ference in the mean levels of GPX and GR in serum and follicu- lar fluid between the placebo and metformin groups (P > 0.05). Conclusion: Our results showed that Metformin reduced oxi- dative stress in women with PCOS by decreasing MDA levels and increasing serum TAC. However, it had no significant ef- fect on GPX, GR, or TAC levels in follicular fluid, suggesting that its antioxidant effects are primarily systemic rather than localized within the follicular environment.