Cardiovascular disease is the most common cause of mortality worldwide, accounting for almost 50% of all deaths globally. Vascular endothelial dysfunction and fibrosis are critical in the pathophysiology of cardiovascular disease. Relaxin, an insulin-like peptide, is known to have beneficial actions in the cardiovascular system through its vasoprotective and anti-fibrotic effects. However, relaxin has several limitations of peptide-based drugs such as poor oral bioavailability, laborious, and expensive to synthesize. This review will focus on recent developments in relaxin mimetics, their pharmacology, associated signalling mechanisms, and their therapeutic potential for the management and treatment of cardiovascular disease.