N‐acetylcysteine (NAC) is a compound whose mechanism of action is intricately linked to the provision of cysteine for glutathione synthesis. It has been used in medicine and has also made significant inroads into sports, as it can modify the levels of several biomarkers, including those of oxidative processes, inflammation and muscle damage after exercise. Because the effectiveness of NAC supplementation is unclear, the primary objective of the present study was to perform a meta‐analysis elucidating how NAC supplementation alters the concentrations of GSH (glutathione), GSSG (glutathione disulfide), TBARS (thiobarbituric acid reactive substances), IL‐6 (interleukin 6), TNF‐α (tumour necrosis factor alpha), CK (creatine kinase), lactate, and muscle soreness after physical exertion. Suitable studies were searched for from February to September 2023, and the results of those included (n = 20) indicate that NAC supplementation significantly diminishes both muscle soreness (p = 0.03; the mean difference (MD) of NAC's effect was −0.43 with a 95% confidence interval (CI), −0.81, −0.04) and lactate concentrations after exercise (p = 0.03; the MD −0.56 mmol/L; 95% CI, −1.07, −0.06). A substantial decrease was observed in concentrations of IL‐6 (p = 0.03; the standardized MD (SMD) was −1.71; 95% CI, −3.26, −0.16) and TBARS (p = 0.02; SMD was −1.03, 95% CI, −1.90, −0.15). Furthermore, an elevation in GSH concentration was observed following supplementation. However, we saw no significant effect of NAC on TNF‐α, CK or GSSG concentrations. NAC supplementation holds promise for attenuating muscle soreness, lactate, TBARS and IL‐6 concentrations and increasing GSH level following physical exertion.