Abstract: Osteoarthritis is a degenerative joint disease characterized by cartilage degradation, synovial inflammation and subchondral bone remodeling. The FOXO3 transcription factor plays critical role in various cellular processes, including apoptosis, autophagy and antioxidant stress responses. This article reviewed the mechanisms of FOXO3 in the pathological progression of osteoarthritis and its condition as potential therapeutic target, exploring the significance of FOXO3 function for developing novel interventions to delay osteoarthritis progression and improve quality of life of patients.