Autophagy is a catabolic process that recycles cellular components and damaged organelles in response to stress, such as nutrient deprivation, viral infection, and genotoxic stress. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are key intracellular signals that sustain autophagy. This review explores the regulatory pathways of autophagy in response to glucose and amino acid deprivation, its connection with metabolic networks and redox homeostasis, and the role of oxidative and nitrosative stress in autophagy. The review also discusses the redox-independent relationship between autophagy and antioxidant response via the p62/Keap1/Nrf2 pathway, and the complex crosstalk between autophagy and DNA damage response (DDR), focusing on pathways activated by ROS and RNS overproduction. The direct and indirect roles of autophagy in DDR are dissected in depth. ROS and RNS are major sources of DNA damage, leading to oxidative stress. Autophagy contributes to clearing irreversibly oxidized biomolecules, making it a part of antioxidant and DNA damage repair systems. The review also addresses how autophagy senses DNA damage and contributes to its repair. Autophagy is considered both a pro-survival mechanism and a type of cell death, playing a crucial role in regulating cell fate upon DNA injury. It can delay apoptotic cell death by supporting DNA repair processes, contributing to chemoresistance in cancer cells. Conversely, in cells with unrepaired DNA and defective apoptosis, autophagy can induce cell death, acting as a tumor suppressor. The review highlights the complex interplay between autophagy and oxidative stress, including the role of ROS in autophagy induction, the mitochondrial origin of ROS, and the role of mitophagy in removing damaged mitochondria. It also discusses the redox signaling in autophagy, the role of NO and nitrosative stress, and the p62/Keap1/Nrf2 system in linking autophagy with redox response. The review concludes that while autophagy is involved in DNA damage repair, the exact mechanisms remain unclear, and further research is needed to fully understand the antioxidant role of autophagy in maintaining genomic stability.Autophagy is a catabolic process that recycles cellular components and damaged organelles in response to stress, such as nutrient deprivation, viral infection, and genotoxic stress. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are key intracellular signals that sustain autophagy. This review explores the regulatory pathways of autophagy in response to glucose and amino acid deprivation, its connection with metabolic networks and redox homeostasis, and the role of oxidative and nitrosative stress in autophagy. The review also discusses the redox-independent relationship between autophagy and antioxidant response via the p62/Keap1/Nrf2 pathway, and the complex crosstalk between autophagy and DNA damage response (DDR), focusing on pathways activated by ROS and RNS overproduction. The direct and indirect roles of autophagy in DDR are dissected in depth. ROS and RNS are major sources of DNA damage, leading to oxidative stress. Autophagy contributes to clearing irreversibly oxidized biomolecules, making it a part of antioxidant and DNA damage repair systems. The review also addresses how autophagy senses DNA damage and contributes to its repair. Autophagy is considered both a pro-survival mechanism and a type of cell death, playing a crucial role in regulating cell fate upon DNA injury. It can delay apoptotic cell death by supporting DNA repair processes, contributing to chemoresistance in cancer cells. Conversely, in cells with unrepaired DNA and defective apoptosis, autophagy can induce cell death, acting as a tumor suppressor. The review highlights the complex interplay between autophagy and oxidative stress, including the role of ROS in autophagy induction, the mitochondrial origin of ROS, and the role of mitophagy in removing damaged mitochondria. It also discusses the redox signaling in autophagy, the role of NO and nitrosative stress, and the p62/Keap1/Nrf2 system in linking autophagy with redox response. The review concludes that while autophagy is involved in DNA damage repair, the exact mechanisms remain unclear, and further research is needed to fully understand the antioxidant role of autophagy in maintaining genomic stability.