Doxorubicin (DOX) is an effective antineoplastic agent used to treat various types of cancers. However, its use is limited by the development of cardiotoxicity, which may result in heart failure. The exact mechanisms underlying DOX-induced cardiotoxicity are not fully understood, but recent studies have shown that endothelial–mesenchymal transition (EndMT) and endothelial damage play a crucial role in this process. EndMT is a biological process in which endothelial cells lose their characteristics and transform into mesenchymal cells, which have a fibroblast-like phenotype. This process has been shown to contribute to tissue fibrosis and remodeling in various diseases, including cancer and cardiovascular diseases. DOX-induced cardiotoxicity has been demonstrated to increase the expression of EndMT markers, suggesting that EndMT may play a critical role in the development of this condition. Furthermore, DOX-induced cardiotoxicity has been shown to cause endothelial damage, leading to the disruption of the endothelial barrier function and increased vascular permeability. This can result in the leakage of plasma proteins, leading to tissue edema and inflammation. Moreover, DOX can impair the production of nitric oxide, endothelin-1, neuregulin, thrombomodulin, thromboxane B2 etc. by endothelial cells, leading to vasoconstriction, thrombosis and further impairing cardiac function. In this regard, this review is devoted to the generalization and structuring of information about the known molecular mechanisms of endothelial remodeling under the action of DOX.