Cerebral ischemia-reperfusion injury can lead to secondary brain damage through complex pathological processes such as ion imbalance, inflammation, mitochondrial dysfunction, oxidative stress, and increased vascular permeability, seriously affecting the prognosis and quality of life of ischemic stroke patients. How to effectively reduce and prevent neurological damage caused by CIRI has become a key and hot topic in CIS research. In recent years, many studies have confirmed that the active ingredients of traditional Chinese medicine can alleviate oxidative stress, inhibit autophagy, regulate cell apoptosis, control neuroinflammation, reduce cell apoptosis index, alleviate neuronal histopathological damage, promote neuronal survival, enhance synaptic plasticity, and play a therapeutic role in CIRI through the PI3K/Akt signaling pathway. In summary, this article provides a review of the PI3K/Akt signaling pathway and its role in CIRI, as well as the research on the regulation of PI3K/Akt signaling by active ingredients in traditional Chinese medicine for the treatment of CIRI. The aim is to provide a theoretical basis for the clinical use of active ingredients in traditional Chinese medicine to alleviate CIRI damage.