Glutathione (GSH) is a tripeptide with multiple biological functions, including protection against reactive oxygen and nitrogen species. This review discusses the mechanisms of GSH's protective role against reactive species and electrophiles, as well as its biosynthesis, hydrolysis, utilization, intracellular compartmentalization, and interorgan transfer. It also covers GSH's involvement in metal homeostasis, glutathione-related enzymes, and glutathioneylation of sulfhydryls. The paper highlights the relationship between GSH homeostasis and pathologies, as well as research tools and pharmacological approaches to manipulate GSH levels. Special attention is given to natural compounds that affect GSH-related processes. The review provides insights into the physiological and biochemical functions of GSH with a focus on human and animal health. GSH is synthesized in two steps: first, γ-glutamylcysteine is formed by γ-glutamylcysteine synthetase, and then glutathione is synthesized by glutathione synthetase. GSH is consumed through oxidation, conjugation, and hydrolysis. It is involved in antioxidant defense systems, detoxification of endogenous and exogenous compounds, and various metabolic processes. GSH is also a reserve form of cysteine, stores and transports nitric oxide, participates in estrogen, leukotriene, and prostaglandin metabolism, and is involved in the reduction of ribonucleotides to deoxyribonucleotides and the maturation of iron-sulfur clusters. GSH is distributed to different intracellular organelles where it plays specific roles in maintaining cellular redox status. In the endoplasmic reticulum, GSH is involved in the formation of intramolecular disulfide bonds, while in the nucleus, it maintains the redox status of sulfhydryl groups in proteins. In mitochondria, GSH is crucial for cell survival, as it protects against oxidative damage and prevents apoptosis. GSH is also involved in the detoxification of reactive oxygen and nitrogen species, and in the metabolism of various xenobiotics. The regulation of GSH levels is controlled by various enzymes, including γ-glutamylcysteine synthetase and glutathione reductase. The Nrf2/Keap1 system is a key regulatory pathway that controls the expression of antioxidant and phase II detoxification enzymes in response to oxidative stress. GSH is also involved in the detoxification of xenobiotics through phase I, II, and III enzymes. The role of GSH in the detoxification of xenobiotics is often direct, without the need for prior activation by phase I enzymes. Glutathioneylation is a process in which GSH forms mixed disulfides with protein thiols, and is involved in the regulation of enzyme activity and certain regulatory pathways. Oxidation of cystGlutathione (GSH) is a tripeptide with multiple biological functions, including protection against reactive oxygen and nitrogen species. This review discusses the mechanisms of GSH's protective role against reactive species and electrophiles, as well as its biosynthesis, hydrolysis, utilization, intracellular compartmentalization, and interorgan transfer. It also covers GSH's involvement in metal homeostasis, glutathione-related enzymes, and glutathioneylation of sulfhydryls. The paper highlights the relationship between GSH homeostasis and pathologies, as well as research tools and pharmacological approaches to manipulate GSH levels. Special attention is given to natural compounds that affect GSH-related processes. The review provides insights into the physiological and biochemical functions of GSH with a focus on human and animal health. GSH is synthesized in two steps: first, γ-glutamylcysteine is formed by γ-glutamylcysteine synthetase, and then glutathione is synthesized by glutathione synthetase. GSH is consumed through oxidation, conjugation, and hydrolysis. It is involved in antioxidant defense systems, detoxification of endogenous and exogenous compounds, and various metabolic processes. GSH is also a reserve form of cysteine, stores and transports nitric oxide, participates in estrogen, leukotriene, and prostaglandin metabolism, and is involved in the reduction of ribonucleotides to deoxyribonucleotides and the maturation of iron-sulfur clusters. GSH is distributed to different intracellular organelles where it plays specific roles in maintaining cellular redox status. In the endoplasmic reticulum, GSH is involved in the formation of intramolecular disulfide bonds, while in the nucleus, it maintains the redox status of sulfhydryl groups in proteins. In mitochondria, GSH is crucial for cell survival, as it protects against oxidative damage and prevents apoptosis. GSH is also involved in the detoxification of reactive oxygen and nitrogen species, and in the metabolism of various xenobiotics. The regulation of GSH levels is controlled by various enzymes, including γ-glutamylcysteine synthetase and glutathione reductase. The Nrf2/Keap1 system is a key regulatory pathway that controls the expression of antioxidant and phase II detoxification enzymes in response to oxidative stress. GSH is also involved in the detoxification of xenobiotics through phase I, II, and III enzymes. The role of GSH in the detoxification of xenobiotics is often direct, without the need for prior activation by phase I enzymes. Glutathioneylation is a process in which GSH forms mixed disulfides with protein thiols, and is involved in the regulation of enzyme activity and certain regulatory pathways. Oxidation of cyst