Ischemic cerebrovascular and cardiovascular diseases in brain and heart tissues caused by hyperlipidemia, blood viscosity, atherosclerosis, hypertension, etc. Have been increasing in morbidity and mortality in the middle-aged and elderly population over several years. In recent years, the Eph/ephrin signaling pathway has been found to have a major role in the processes of neurogenesis, synaptic plasticity, and angiogenesis, which is likely a key pathway in the modulation of neurological and cardiac functions. Therefore, an in-depth understanding of the role of the Eph/Ephrin signaling pathway in pathophysiological processes will be the emphasis of future research. In ischemic cardiovascular and cerebrovascular diseases, in particular, the development of effective treatment to modulate the Eph/Ephrin signaling pathway to promote neural and vascular repair and regeneration is of great clinical significance and social value. In this study, the role of the Eph/ephrin signaling pathway in ischemic cerebrovascular and cardiovascular diseases is reviewed.