Endothelins are small 21 amino acid peptides that interact with G-protein-coupled receptors. They are highly conserved across species and play important roles in vascular biology as well as in disease development and progression. Endothelins, mainly endothelin-1 and endothelin-2, are intricately involved in ovarian function and metabolism. These two peptides differ only in two amino acids but are encoded by different genes, which suggests an independent regulation and a cell-specific mode of expression. This review aims to comprehensively discuss the distinct regulation and roles of endothelin-1 and endothelin-2 regarding corpus luteum function throughout its life span.