Objective: To elucidate how indomethacin may slow the progression of osteoarthritis (OA). Methods: Chondrocytes were treated with IL-1β (10 ng/mL) for 12 hours to create an in vitro model of OA. Following this, 10 µM of indomethacin was added to the IL-1β-treated chondrocytes for an additional 4 hours to evaluate its effects on inflammation, anabolism, catabolism, apoptosis, and autophagy using ELISA, western blot, immunofluorescence and flow cytometry, respectively. Results: IL-1β significantly stimulated inflammatory responses, hampered anabolic processes, induced catabolic activity, accelerated apoptosis, and inhibited autophagy in chondrocytes, as well as activated the PI3K/AKT/mTOR signaling pathway. However, treatment with indomethacin reversed the effects of IL-1β stimulation on chondrocytes and simultaneously suppressed the activation of the PI3K/AKT/mTOR signaling pathway. Conclusions: Our findings indicate the mechanism of action of indomethacin in mitigating OA progression, indicating that it can inactivate the PI3K/AKT/mTOR signaling pathway, thereby regulating inflammation, metabolism, apoptosis, and autophagy in chondrocytes, which attenuates the development of OA.