In physiological conditions, spermatozoa produce little ROS, which are required for sperm physiology (sperm hyperactivation, capacitation, acrosome reaction) and also for natural fertilization . Many environmental, physiological, and genetic factors have been implicated with sperm functions and infertility . ROS may have either endogenous or exogenous origin and may cause defective spermatogenesis and male infertility . Oxidative stress markers, i.e. total antioxidant capacity (TAC) and malondialdehyde (MDA), as well as hormonal profile (LH, FSH, Testosterone and Prolactin) were determined by ELISA kit. Of the 777 records identified in the search, 16 studies met the inclusion and exclusion criteria. We aimed to evaluate the current evidence on the benefits of NAC supplementation on physical performance and laboratory biomarkers in adult men. LC/LAC and NAC showed a greater improvement in sperm motility and normal morphology. Badawy et al. reported that NAC induced ovulation in PCOS patients through increasing insulin sensitivity(Reference Badawy, State and Abdelgawad13). It must be noted that the GSH levels might be effective in the relationship between NAC and reproductive biomarkers(Reference Atkuri, Mantovani and Herzenberg50). Therefore, NAC, through decreasing lipid peroxidation, could have beneficial effects on reproductive biomarkers. Regarding TT, studies with shorter duration had smaller sample sizes than studies with longer duration studies. In other investigated variables, extending supplementation duration was ineffective in the overall results. NAC supplementation for ≥ 8 weeks led to a significant decrease in TT. TNF-α and IL-6 levels could be positively impressed by NAC(Reference Faghfouri, Zarezadeh and Tavakoli-Rouzbehani6). This medication is an acetylated variant of l-cysteine, a great source of sulfhydryl groups. N-acetylcysteine (NAC) is a safe, economic and affordable drug which is used for the stimulation of ovulation(Reference Ghomian, Khadem and Moeindarbari5). The small-study effect was evaluated by the formal tests of Egger’s and Begg’s. To detect potential sources of heterogeneity, subgroup analyses were performed according to the predefined variables, including duration of the intervention, NAC dosage, study location and the type of control. If heterogeneity was not significant, the fixed-effects model was employed to estimate the overall effect size. Risk bias assessments were conducted independently by two reviewers. If the study contains a methodological defect that may affect its findings, the study was given a ‘high risk’ score; if there was no defect for that domain, a ‘low risk’ score; if the information was insufficient to determine the effect, an ‘uncertain risk’ score. The tool consists of seven domains, including random sequence generation, allocation concealment, performance bias, reporting bias, detection bias, attrition bias and other sources of bias. These results indicate that supplemental selenium and N-acetyl-cysteine improve semen quality. NAC is a precursor of the detoxifying enzyme glutathione. Selenium is needed for the detoxifying enzyme glutathione peroxidase. NAC effects on GSH rely on the presence of the free sulfyhydryl group as a ready source of reducing equivalents to quench radical species . Both exogenous and endogenous ROS can induce sperm DNA damage in vitro, confirming that ROS may play a role in the etiology of sperm DNA damage in infertile men 30, 31 . Relationship between sperm DNA fragmentation and sperm motility or abnormality.