Liver diseases markedly contribute to the global burden of mortality and morbidity. The pathogenesis of alcohol- and non-alcohol-induced liver diseases is complex, and many factors have been described to contribute to the progressive loss of liver functions, including the over-generation of reactive oxygen species. Glutathione (GSH) is the most important low-molecular-weight antioxidant synthesized in cells, as it is a reducing molecule which can react to oxygen species by neutralizing the unpaired electrons that make them highly reactive and dangerous. ROS over-production impairs the intracellular GSH homeostasis, leading to GSH deficiency, a pathophysiological hallmark in alcoholic and non-alcoholic liver diseases.Judging on the basis of the evidence obtained from experimental research and previous clinical studies, GSH administration seems to be a promising strategy to recover oxidative stress-induced liver damages in alcoholic and non-alcoholic liver diseases.