Abstract: Stroke is the second leading cause of disability and death globally, placing a huge burden on individuals and society. There are approximately 14 million strokes worldwide, of which about 85% are ischemic strokes, with large vessel occlusions accounting for 10% to 20%. Currently the only effective drug treatment is limited to the recombinant tissue plasminogen activator (tPA). However, due to the narrow time window of tPA and the low recanalization rate, this treatment is only suitable for a small number of stroke patients. Therefore, the development of new therapeutic drugs or combination therapies is an urgent need. Natural medicine extract or combinations of natural medicines have made great progress in the treatment of stroke. Natural medicines derived from traditional Chinese herbs have many beneficial effects such as antioxidation, anti-inflammation and anti-apoptosis, and have the potential to treat stroke. This review mainly summarizes the pathogenesis of acute ischemic stroke and the research progress of small-molecule natural medicines potentially used in cerebral ischemic stroke.