Ovarian ferroptosis, a type of iron-dependent programmed cell death, is involved in the pathogenesis of polycystic ovary syndrome (PCOS). This study demonstrates that increased ferroptosis occurs in the ovaries of PCOS patients and in a DHEA-induced PCOS rat model. Ferroptosis was characterized by elevated levels of Fe²⁺ and malondialdehyde (MDA), along with decreased expression of ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4), and increased expression of nuclear receptor coactivator 4 (NCOA4). DHT was shown to induce ferroptosis via NCOA4-dependent ferritinophagy. Treatment with the ferroptosis inhibitor Fer-1 ameliorated PCOS traits, including impaired glucose tolerance, irregular estrous cycles, reproductive hormone dysfunction, hyperandrogenism, polycystic ovaries, anovulation, and oocyte quality. Conversely, treatment with the ferroptosis inducer RSL3 resulted in polycystic ovaries and hyperandrogenism. These findings suggest that androgen-induced ovarian ferroptosis plays a role in PCOS progression and may be a potential therapeutic target. The study also reveals a self-perpetuating cycle between hyperandrogenism and ferroptosis in PCOS, which could be a new insight for treatment. The results indicate that ovarian ferroptosis is a critical factor in PCOS development, and ferroptosis inhibitors may offer a promising treatment option for PCOS.Ovarian ferroptosis, a type of iron-dependent programmed cell death, is involved in the pathogenesis of polycystic ovary syndrome (PCOS). This study demonstrates that increased ferroptosis occurs in the ovaries of PCOS patients and in a DHEA-induced PCOS rat model. Ferroptosis was characterized by elevated levels of Fe²⁺ and malondialdehyde (MDA), along with decreased expression of ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4), and increased expression of nuclear receptor coactivator 4 (NCOA4). DHT was shown to induce ferroptosis via NCOA4-dependent ferritinophagy. Treatment with the ferroptosis inhibitor Fer-1 ameliorated PCOS traits, including impaired glucose tolerance, irregular estrous cycles, reproductive hormone dysfunction, hyperandrogenism, polycystic ovaries, anovulation, and oocyte quality. Conversely, treatment with the ferroptosis inducer RSL3 resulted in polycystic ovaries and hyperandrogenism. These findings suggest that androgen-induced ovarian ferroptosis plays a role in PCOS progression and may be a potential therapeutic target. The study also reveals a self-perpetuating cycle between hyperandrogenism and ferroptosis in PCOS, which could be a new insight for treatment. The results indicate that ovarian ferroptosis is a critical factor in PCOS development, and ferroptosis inhibitors may offer a promising treatment option for PCOS.