Ischemia–reperfusion (I/R) injury remains a major clinical challenge, where inadequate revascularization following ischemic insult leads to tissue damage and impaired functional recovery. While therapeutic angiogenesis has been extensively explored, the discovery of small molecules that selectively promote functional revascularization without inducing pathological angiogenesis remains limited. Chalcone derivatives represent a structurally versatile scaffold with context-dependent vascular activities; however, their potential to promote revascularization has not been systematically explored.