Acute kidney injury (AKI) is a systemic inflammatory disease with limited treatment options. Irisin is a novel actin protein produced by skeletal muscle movement and exerts anti-inflammatory, anti-apoptotic, and antioxidant effects by participating in multiple signaling pathways. In recent years, the protective effect of irisin on AKI has attracted much attention, and its regulatory mechanism involves a complex network of signaling pathways, which can reduce oxidative stress, inhibit apoptosis, inhibit inflammation, and inhibit ferroptosis under pathological conditions. This pathway alleviates kidney injury by enhancing the metabolic reprogramming of tubular cells while attenuating fibrosis. Irisin is expected to be a new treatment option for AKI.