With the rapid development of tumor chemotherapy, the overall survival of tumor patients has been continuously prolonged. However, the cardiovascular toxic side effects caused by chemotherapy seriously limit the effectiveness of tumor treatment, and have become a high-risk factor affecting the quality of life and survival rate of patients. Among them, chemotherapy-related vascular endothelial injury can disrupt vascular homeostasis, which serves as the pathological basis of cardiovascular toxic side effects such as acute vascular events (vasospasm, acute myocardial infarction, stroke, etc.), atherosclerosis, hypertension, and aneurysms. Exploring the mechanisms and protective strategies of chemotherapy-related vascular endothelial injury is of great clinical significance. This review aims to summarize the latest progress in the mechanisms of chemotherapy-associated vascular endothelial injury and related protective strategies.