The transcription factor FoxO3a plays a crucial role in the process of cells adapting to various stress conditions. Multiple post - translational modifications and epigenetic mechanisms work together to precisely regulate the activity of FoxO3a, influencing its subcellular localization, stability, interactions with other proteins, DNA - binding affinity, and transcriptional regulatory capacity. Under different chemical signal stimuli and subcellular environments, the activation of FoxO3a triggered by oxidative stress can initiate diverse transcriptional programs, which are essential for the body to resist oxidative damage. In the development and progression of inflammatory diseases, FoxO3a exerts an important function by regulating the expression levels of antioxidant enzymes and participating in key physiological processes such as programmed cell death. This article comprehensively reviews the structural characteristics, mechanism of action of FoxO3a, as well as its functions in regulating antioxidant enzymes and programmed cell death. The aim is to deeply explore the potential of FoxO3a as a potential therapeutic target for preventing and treating damages such as inflammatory diseases caused by cellular stress.