Polycystic ovary syndrome (PCOS) affects 6–20% of reproductive-aged women and is associated with increased risks of metabolic syndrome, type 2 diabetes, cardiovascular diseases, mood disorders, endometrial cancer, and non-alcoholic fatty liver disease. While genetic studies have identified susceptibility loci accounting for ~10% of PCOS heritability, the etiology remains unclear. This review explores the role of epigenetic changes and circadian clock gene modifications in PCOS pathogenesis. Epigenetic alterations, including DNA methylation, histone modifications, and non-coding RNA changes, have been observed in PCOS-related diseases. Animal models show that prenatal exposure to androgens or anti-Müllerian hormone can lead to PCOS-like phenotypes in subsequent generations, indicating epigenetic programming. In humans, epigenetic changes have been found in peripheral blood mononuclear cells, adipose tissue, granulosa cells, and liver of women with PCOS. The genome of women with PCOS is globally hypomethylated, with specific genes involved in hormonal regulation, inflammation, lipid and glucose metabolism showing hypomethylation or hypermethylation. Sleep disorders are common in women with PCOS, and disruptions in clock gene expression patterns have been observed in their PBMCs or granulosa cells. Epigenetic changes hold promise as diagnostic biomarkers, but distinguishing whether they are causes or consequences of PCOS remains a challenge. Targeting epigenetic modifications could lead to precision medicine approaches for PCOS, including lifestyle interventions and drug therapies. However, data from large, well-characterized PCOS cohorts are still lacking. Understanding the interplay between genetics, epigenetics, and circadian rhythms may provide valuable insights for early diagnosis and therapeutic strategies in PCOS. Circadian clock genes, such as CLOCK, BMAL1, PER, and CRY, are involved in regulating physiological processes and have been implicated in PCOS. Studies show that circadian clock genes are dysregulated in women with PCOS, with reduced expression of core clock genes. Circadian rhythm disruptions are associated with sleep disorders and metabolic dysfunction in PCOS. The circadian clock may play a role in the pathogenesis of PCOS, with altered clock gene expression linked to androgen production and metabolic disturbances. Future research should focus on identifying specific epigenetic changes in PCOS to improve early diagnosis and develop targeted therapies. Epigenetic modifications, including DNA methylation, can be influenced by lifestyle factors such as physical activity and diet, and may be reversible, offering potential targets for PCOS treatment. Drugs like metformin and S-adenosylmethionine have shown potential in modulating epigenetic processes in PCOS. Overall, epigenetic and circadian clock mechanisms are emerging as important areas of research for understanding and managing PCOS.Polycystic ovary syndrome (PCOS) affects 6–20% of reproductive-aged women and is associated with increased risks of metabolic syndrome, type 2 diabetes, cardiovascular diseases, mood disorders, endometrial cancer, and non-alcoholic fatty liver disease. While genetic studies have identified susceptibility loci accounting for ~10% of PCOS heritability, the etiology remains unclear. This review explores the role of epigenetic changes and circadian clock gene modifications in PCOS pathogenesis. Epigenetic alterations, including DNA methylation, histone modifications, and non-coding RNA changes, have been observed in PCOS-related diseases. Animal models show that prenatal exposure to androgens or anti-Müllerian hormone can lead to PCOS-like phenotypes in subsequent generations, indicating epigenetic programming. In humans, epigenetic changes have been found in peripheral blood mononuclear cells, adipose tissue, granulosa cells, and liver of women with PCOS. The genome of women with PCOS is globally hypomethylated, with specific genes involved in hormonal regulation, inflammation, lipid and glucose metabolism showing hypomethylation or hypermethylation. Sleep disorders are common in women with PCOS, and disruptions in clock gene expression patterns have been observed in their PBMCs or granulosa cells. Epigenetic changes hold promise as diagnostic biomarkers, but distinguishing whether they are causes or consequences of PCOS remains a challenge. Targeting epigenetic modifications could lead to precision medicine approaches for PCOS, including lifestyle interventions and drug therapies. However, data from large, well-characterized PCOS cohorts are still lacking. Understanding the interplay between genetics, epigenetics, and circadian rhythms may provide valuable insights for early diagnosis and therapeutic strategies in PCOS. Circadian clock genes, such as CLOCK, BMAL1, PER, and CRY, are involved in regulating physiological processes and have been implicated in PCOS. Studies show that circadian clock genes are dysregulated in women with PCOS, with reduced expression of core clock genes. Circadian rhythm disruptions are associated with sleep disorders and metabolic dysfunction in PCOS. The circadian clock may play a role in the pathogenesis of PCOS, with altered clock gene expression linked to androgen production and metabolic disturbances. Future research should focus on identifying specific epigenetic changes in PCOS to improve early diagnosis and develop targeted therapies. Epigenetic modifications, including DNA methylation, can be influenced by lifestyle factors such as physical activity and diet, and may be reversible, offering potential targets for PCOS treatment. Drugs like metformin and S-adenosylmethionine have shown potential in modulating epigenetic processes in PCOS. Overall, epigenetic and circadian clock mechanisms are emerging as important areas of research for understanding and managing PCOS.