Puerarin is an isoflavone compound derived from Pueraria lobata in traditional Chinese medicine. Accumulating evidence has indicated that puerarin demonstrates multiple pharmacological effects and exhibits treatment potential for various neurological disorders. Based on the latest research progress on puerarin as a neuroprotective agent, its pharmacological activity, molecular mechanism, and therapeutic application were systematically reviewed with emphasis on pre-clinical studies. The related information was extracted and compiled from major scientific databases, including PubMed, ScienceDirect, SpringerLink, and Chinese National Knowledge Infrastructure, using 'Puerarin', 'Neuroprotection', 'Apoptosis', 'Autophagy', 'Antioxidant', 'Mitochondria', 'Anti-inflammation' as keywords. This review complied with The Preferred Reporting Items for Systematic Reviews criteria. Forty-three articles met established inclusion and exclusion criteria. Puerarin has shown neuroprotective effects against a variety of neurological disorders, including ischemic cerebrovascular disease, subarachnoid hemorrhage, epilepsy, cognitive disorders, traumatic brain injury, Parkinson's disease, Alzheimer's disease, anxiety, depression, diabetic neuropathy, and neuroblastoma/glioblastoma. Puerarin demonstrates anti-apoptosis, proinflammatory mediator inhibitory, autophagy regulatory, anti-oxidative stress, mitochondria protection, Ca²⁺ influx inhibitory, and anti-neurodegenerative activities. Puerarin exerts noticeable neuroprotective effects on various models of neurological disorders in vivo (animal). This review will contribute to the development of puerarin as a novel clinical drug candidate for the treatment of neurological disorders. However, well-designed, high-quality, large-scale, multicenter randomized clinical studies are needed to determine the safety and clinical utility of puerarin in patients with neurological disorders.