BACKGROUNDTB remains a major global health challenge. Glutathione (GSH) and -acetylcysteine (NAC) have been proposed as adjunctive therapies with potential clinical and immunomodulatory benefits. This systematic review aims to evaluate the efficacy, safety, and immunomodulatory effects of GSH and NAC as adjunctive therapies in TB management.METHODSPubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched until October 15, 2024. We included studies assessing the efficacy of GSH and NAC in TB management, focusing on clinical outcomes such as lung function recovery, sputum conversion, hepatoprotection, and immune response modulation. The quality of the studies was assessed using the Cochrane Risk of Bias tool.RESULTSEight controlled trials were included. GSH and NAC significantly improved lung function accelerated sputum conversion, and provided hepatoprotective effects. GSH, particularly in its liposomal form, enhanced immune responses by modulating cytokine levels and reducing oxidative stress. Most adverse effects reported were mild and manageable, indicating a favourable safety profile for both agents.CONCLUSIONSGSH and NAC show promise as adjunctive therapies in TB management, demonstrating improvements in lung function, sputum conversion, and hepatoprotection while also enhancing immune responses..