Oxidative stress (OS) is a major contributor to male infertility, disrupting the balance between reactive oxygen species (ROS) and antioxidants, which negatively affects sperm function and viability. OS causes molecular changes in sperm, including DNA damage, lipid peroxidation, and protein expression alterations, further compromising fertility. Diagnostic tools assess OS markers, antioxidant levels, and intracellular ROS concentrations to aid in diagnosing male infertility. Treatment options include empirical drugs, antioxidants, nanoantioxidants, and lifestyle modifications. Addressing the root causes of OS and implementing targeted interventions can optimize treatment outcomes and improve conception chances for couples with infertility. OS is influenced by various exogenous and endogenous factors, including environmental pollution, bacterial/viral infections, obesity, tobacco and alcohol use, and varicocele. Leukocytes in seminal plasma, particularly polymorphonuclear leukocytes and macrophages, contribute to ROS production, leading to OS. Spermatozoa are highly susceptible to oxidation due to their high unsaturated fatty acid content and low antioxidant enzyme levels. Increased ROS levels impair sperm motility and attachment to the oocyte, while reduced antioxidant capacity exacerbates DNA damage and chromatin abnormalities. Diagnostic tests for OS include chemiluminescence, total antioxidant capacity (TAC), oxidation-reduction potential (ORP), nitroblue tetrazolium (NBT), cytochrome c reduction test, and electron spin resonance (ESR). Flow cytometry using DCFDA and DHE dyes measures intracellular ROS levels. These tests help assess the extent of OS and guide treatment decisions. Therapeutic approaches include empirical medical therapy, antioxidant treatment, and nanoantioxidants. Antioxidants like vitamin C, vitamin E, and CoQ10 improve sperm parameters and reduce ROS levels. Nanoantioxidants, such as zinc oxide and cerium dioxide nanoparticles, offer enhanced bioavailability and targeted delivery, improving sperm viability and reducing apoptosis. Hormonal therapies, including gonadotropins and androgens, are used to address hormonal imbalances in idiopathic infertility. Lifestyle modifications, such as adopting a Mediterranean diet, weight loss, regular exercise, quitting smoking, and limiting alcohol consumption, can reduce OS and improve sperm parameters. Assisted reproductive techniques (ARTs) like IUI, IVF, and ICSI are used to treat male infertility, with ICSI being particularly effective for severe cases. OS levels can predict IVF and ICSI outcomes, highlighting the importance of managing OS in ART practices. Overall, a combination of medical, antioxidant, and lifestyle interventions is crucial for effectively managing OS-associated male infertility.Oxidative stress (OS) is a major contributor to male infertility, disrupting the balance between reactive oxygen species (ROS) and antioxidants, which negatively affects sperm function and viability. OS causes molecular changes in sperm, including DNA damage, lipid peroxidation, and protein expression alterations, further compromising fertility. Diagnostic tools assess OS markers, antioxidant levels, and intracellular ROS concentrations to aid in diagnosing male infertility. Treatment options include empirical drugs, antioxidants, nanoantioxidants, and lifestyle modifications. Addressing the root causes of OS and implementing targeted interventions can optimize treatment outcomes and improve conception chances for couples with infertility. OS is influenced by various exogenous and endogenous factors, including environmental pollution, bacterial/viral infections, obesity, tobacco and alcohol use, and varicocele. Leukocytes in seminal plasma, particularly polymorphonuclear leukocytes and macrophages, contribute to ROS production, leading to OS. Spermatozoa are highly susceptible to oxidation due to their high unsaturated fatty acid content and low antioxidant enzyme levels. Increased ROS levels impair sperm motility and attachment to the oocyte, while reduced antioxidant capacity exacerbates DNA damage and chromatin abnormalities. Diagnostic tests for OS include chemiluminescence, total antioxidant capacity (TAC), oxidation-reduction potential (ORP), nitroblue tetrazolium (NBT), cytochrome c reduction test, and electron spin resonance (ESR). Flow cytometry using DCFDA and DHE dyes measures intracellular ROS levels. These tests help assess the extent of OS and guide treatment decisions. Therapeutic approaches include empirical medical therapy, antioxidant treatment, and nanoantioxidants. Antioxidants like vitamin C, vitamin E, and CoQ10 improve sperm parameters and reduce ROS levels. Nanoantioxidants, such as zinc oxide and cerium dioxide nanoparticles, offer enhanced bioavailability and targeted delivery, improving sperm viability and reducing apoptosis. Hormonal therapies, including gonadotropins and androgens, are used to address hormonal imbalances in idiopathic infertility. Lifestyle modifications, such as adopting a Mediterranean diet, weight loss, regular exercise, quitting smoking, and limiting alcohol consumption, can reduce OS and improve sperm parameters. Assisted reproductive techniques (ARTs) like IUI, IVF, and ICSI are used to treat male infertility, with ICSI being particularly effective for severe cases. OS levels can predict IVF and ICSI outcomes, highlighting the importance of managing OS in ART practices. Overall, a combination of medical, antioxidant, and lifestyle interventions is crucial for effectively managing OS-associated male infertility.