This review explores the intricate relationship between oxidative stress and autophagy, highlighting their roles in cellular homeostasis and stress response. Autophagy, a catabolic process that recycles damaged cellular components, is activated in response to various stress conditions such as nutrient deprivation, viral infection, and genotoxic stress. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a crucial role in this process, acting as key intracellular signal transducers. The review discusses the regulatory pathways of autophagy in response to glucose and amino acid deprivation, emphasizing its tight interconnection with metabolic networks and redox homeostasis. It also examines the harmful effects of oxidative and nitrosative stress on cellular biomolecules and signal mediators through reversible posttranslational modifications of thiol-containing proteins. Additionally, the redox-independent relationship between autophagy and the antioxidant response, mediated by the p62/Keap1/Nrf2 pathway, is addressed. The complex crosstalk between autophagy and the DNA damage response (DDR) is further explored, focusing on the pathways activated upon ROS and RNS overproduction. The direct and indirect roles of autophagy in DDR are discussed in detail, including its contribution to DNA damage repair and its impact on cell fate. The review concludes by highlighting the multifaceted roles of autophagy in maintaining cellular integrity and survival under oxidative stress conditions.This review explores the intricate relationship between oxidative stress and autophagy, highlighting their roles in cellular homeostasis and stress response. Autophagy, a catabolic process that recycles damaged cellular components, is activated in response to various stress conditions such as nutrient deprivation, viral infection, and genotoxic stress. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a crucial role in this process, acting as key intracellular signal transducers. The review discusses the regulatory pathways of autophagy in response to glucose and amino acid deprivation, emphasizing its tight interconnection with metabolic networks and redox homeostasis. It also examines the harmful effects of oxidative and nitrosative stress on cellular biomolecules and signal mediators through reversible posttranslational modifications of thiol-containing proteins. Additionally, the redox-independent relationship between autophagy and the antioxidant response, mediated by the p62/Keap1/Nrf2 pathway, is addressed. The complex crosstalk between autophagy and the DNA damage response (DDR) is further explored, focusing on the pathways activated upon ROS and RNS overproduction. The direct and indirect roles of autophagy in DDR are discussed in detail, including its contribution to DNA damage repair and its impact on cell fate. The review concludes by highlighting the multifaceted roles of autophagy in maintaining cellular integrity and survival under oxidative stress conditions.