Ischemic brain injury is a prevalent disease with high disability and mortality, but no efficient therapeutics for the disease are currently available mainly due to the narrow therapeutic window. The treatment of cerebrovascular disease by using herbal medicine has been applied for a long time, from which large amounts of medical experience and knowledge have been accumulated. Numerous natural bioactive compounds extracted from Chinese medicines exhibit neuroprotective activities, especially protecting the brain from ischemic injury. This review summarizes the mechanisms underlying cerebral ischemic pathophysiology, including excitotoxicity, generation of free radical, inflammation, astrocytic influence, apoptosis, blood-brain barrier dysfunction, and discusses neuroprotective activities of the representative natural bioactive compounds extracted from traditional medicinal herbs, with targeting one or more signal molecules. Confirmation of potential neuroprotective activities of bioactive compounds derived from Chinese medicine in ischemic stroke treatment is discussed.