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Stroke is one of the leading causes of death and disability in adults worldwide, resulting in huge social and financial burdens. Extracts from herbs, especially those used in Chinese medicine, have emerged as new pharmaceuticals for stroke treatment. Here we review the evidence from preclinical studies investigating neuroprotective properties of Chinese medicinal compounds through their application in acute and subacute phases of ischemic stroke, and highlight potential mechanisms underlying their therapeutic effects. It is noteworthy that many herbal compounds have been shown to target multiple mechanisms and in combinations may exert synergistic effects on signaling pathways, thereby attenuating multiple aspects of ischemic pathology. We conclude the paper with a general discussion of the prospects for novel natural compound-based regimens against stroke.