Mitochondrial glutathione (mGSH) is a key antioxidant that maintains the mitochondrial redox environment, preventing oxidative damage and cell death. It is synthesized in the cytosol and transported into mitochondria via specific carriers, such as the dicarboxylate and 2-oxoglutarate carriers. mGSH plays a critical role in detoxifying reactive oxygen species (ROS), protecting mitochondrial membranes, and maintaining mitochondrial function. It is also involved in various physiological processes, including the metabolism of xenobiotics, thiol disulfide exchange, and cellular signaling. mGSH is essential for maintaining the redox balance in mitochondria, which are the primary site of ROS production. Mitochondrial dysfunction can lead to oxidative stress, which is implicated in various pathologies, including hypoxia, ischemia/reperfusion injury, aging, liver diseases, and neurodegenerative disorders. mGSH depletion has been linked to increased susceptibility to oxidative stress and cell death, particularly in conditions such as alcohol-induced liver injury and neurodegenerative diseases like Alzheimer's disease (AD). In AD, mGSH depletion contributes to oxidative stress and mitochondrial dysfunction, which are key factors in disease progression. mGSH levels are also critical in protecting against drug-induced toxicity, such as that caused by acetaminophen overdose. Strategies to restore mGSH levels or prevent its depletion may be therapeutic in various pathologies. In neurologic disorders, mGSH is essential for protecting neurons from oxidative damage. In Parkinson's disease, mGSH depletion is associated with mitochondrial dysfunction and cell death. mGSH plays a dual role in promoting mitochondrial membrane permeabilization and cell death, as well as in maintaining redox balance. Overall, mGSH is a critical antioxidant that maintains mitochondrial function and protects against oxidative stress in various pathologic settings. Its regulation is essential for cellular survival and the prevention of disease.Mitochondrial glutathione (mGSH) is a key antioxidant that maintains the mitochondrial redox environment, preventing oxidative damage and cell death. It is synthesized in the cytosol and transported into mitochondria via specific carriers, such as the dicarboxylate and 2-oxoglutarate carriers. mGSH plays a critical role in detoxifying reactive oxygen species (ROS), protecting mitochondrial membranes, and maintaining mitochondrial function. It is also involved in various physiological processes, including the metabolism of xenobiotics, thiol disulfide exchange, and cellular signaling. mGSH is essential for maintaining the redox balance in mitochondria, which are the primary site of ROS production. Mitochondrial dysfunction can lead to oxidative stress, which is implicated in various pathologies, including hypoxia, ischemia/reperfusion injury, aging, liver diseases, and neurodegenerative disorders. mGSH depletion has been linked to increased susceptibility to oxidative stress and cell death, particularly in conditions such as alcohol-induced liver injury and neurodegenerative diseases like Alzheimer's disease (AD). In AD, mGSH depletion contributes to oxidative stress and mitochondrial dysfunction, which are key factors in disease progression. mGSH levels are also critical in protecting against drug-induced toxicity, such as that caused by acetaminophen overdose. Strategies to restore mGSH levels or prevent its depletion may be therapeutic in various pathologies. In neurologic disorders, mGSH is essential for protecting neurons from oxidative damage. In Parkinson's disease, mGSH depletion is associated with mitochondrial dysfunction and cell death. mGSH plays a dual role in promoting mitochondrial membrane permeabilization and cell death, as well as in maintaining redox balance. Overall, mGSH is a critical antioxidant that maintains mitochondrial function and protects against oxidative stress in various pathologic settings. Its regulation is essential for cellular survival and the prevention of disease.