Abstract: Recent studies showed that energy metabolism disorder was an important initiating factor of ischemic brain injury, which leads to oxidative stress, neuroinflammation, the activation of glutamate receptor, calcium overload, and apoptosis and other pathological events. Experimental and clinical studies have found that berberine can be used in the treatment of ischemic stroke, whose possible mechanism is to activate AMP-activated protein kinase and its downstream targets, including nuclear factor E2-related factor 2, nuclear factor-κB, phosphoinositide 3-kinase/protein kinase B and mammalian target of rapamycin, so as to improve oxidative stress, neuroinflammation, glutamate excitotoxicity, apoptosis, promote autophagy and angiogenesis, providing a strong basis for the clinical application of berberine in the prevention and treatment of ischemic stroke.