The article reviews the role of redox homeostasis and the Nuclear factor-E2-related factor 2 (Nrf2) pathway in male infertility. Male infertility, affecting over 12% of couples globally, is often caused by male factors. Oxidative stress (OS) and chronic inflammation are key mechanisms leading to sperm membrane and DNA damage, RNA processing disruption, and telomere destruction. Nrf2, an endogenous antioxidant factor, regulates genes to maintain redox balance and is crucial for spermatogenesis and sperm quality. The Keap1-Nrf2 antioxidant pathway, involving Nrf2 activation under oxidative stress, plays a vital role in cellular defense against OS. Studies show that low Nrf2 levels and antioxidant deficiencies are associated with poor sperm quality. Nrf2 knockout mice exhibit severe age-related spermatogenetic impairment, while Nrf2 activation in response to OS enhances antioxidant enzyme expression and protects against oxidative damage. Compounds targeting the Nrf2 pathway, such as hydroxytyrosol, decursin, carvacrol, and melatonin, have shown potential in improving male fertility by modulating OS and antioxidant responses. The article concludes that upregulating the Nrf2 pathway can be a promising therapeutic approach to improve male fertility.The article reviews the role of redox homeostasis and the Nuclear factor-E2-related factor 2 (Nrf2) pathway in male infertility. Male infertility, affecting over 12% of couples globally, is often caused by male factors. Oxidative stress (OS) and chronic inflammation are key mechanisms leading to sperm membrane and DNA damage, RNA processing disruption, and telomere destruction. Nrf2, an endogenous antioxidant factor, regulates genes to maintain redox balance and is crucial for spermatogenesis and sperm quality. The Keap1-Nrf2 antioxidant pathway, involving Nrf2 activation under oxidative stress, plays a vital role in cellular defense against OS. Studies show that low Nrf2 levels and antioxidant deficiencies are associated with poor sperm quality. Nrf2 knockout mice exhibit severe age-related spermatogenetic impairment, while Nrf2 activation in response to OS enhances antioxidant enzyme expression and protects against oxidative damage. Compounds targeting the Nrf2 pathway, such as hydroxytyrosol, decursin, carvacrol, and melatonin, have shown potential in improving male fertility by modulating OS and antioxidant responses. The article concludes that upregulating the Nrf2 pathway can be a promising therapeutic approach to improve male fertility.