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.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of Tsinghua University Press. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).