Ferroptosis is a form of programmed cell death distinct from apoptosis, autophagy, and necrosis, and it is associated with various physiological and pathological processes, including tumorigenesis, neurodegeneration, senescence, blood diseases, kidney disorders, and ischemia-reperfusion injuries. This review focuses on the interaction between ferroptosis and antioxidant systems, particularly the role of transcription factors in regulating ferroptosis. Ferroptosis is characterized by iron accumulation and the production of lipid peroxides, leading to cell membrane damage and ultimately cell death. The control of lipid peroxidation is a key regulator of ferroptosis, and the accumulation of iron and lipid-derived reactive oxygen species (ROS) are crucial factors in this process. The review discusses the metabolic pathways involved in ferroptosis, including the role of iron, lipid peroxidation, and the regulation by transcription factors. It also highlights the importance of redox homeostasis and antioxidant systems in modulating ferroptosis, emphasizing the involvement of enzymes such as glutathione peroxidase 4 (GPX4) and glutathione (GSH). The review further explores the relationship between ferroptosis and various diseases, such as aging, cancer, leukemia, heart failure, and neurodegenerative disorders, and discusses potential therapeutic strategies targeting ferroptosis.Ferroptosis is a form of programmed cell death distinct from apoptosis, autophagy, and necrosis, and it is associated with various physiological and pathological processes, including tumorigenesis, neurodegeneration, senescence, blood diseases, kidney disorders, and ischemia-reperfusion injuries. This review focuses on the interaction between ferroptosis and antioxidant systems, particularly the role of transcription factors in regulating ferroptosis. Ferroptosis is characterized by iron accumulation and the production of lipid peroxides, leading to cell membrane damage and ultimately cell death. The control of lipid peroxidation is a key regulator of ferroptosis, and the accumulation of iron and lipid-derived reactive oxygen species (ROS) are crucial factors in this process. The review discusses the metabolic pathways involved in ferroptosis, including the role of iron, lipid peroxidation, and the regulation by transcription factors. It also highlights the importance of redox homeostasis and antioxidant systems in modulating ferroptosis, emphasizing the involvement of enzymes such as glutathione peroxidase 4 (GPX4) and glutathione (GSH). The review further explores the relationship between ferroptosis and various diseases, such as aging, cancer, leukemia, heart failure, and neurodegenerative disorders, and discusses potential therapeutic strategies targeting ferroptosis.