Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality worldwide. Recent advancements in regenerative medicine have unveiled the promising roles of secretome and exosomes in the treatment of CVDs. In this article, we aim to understand the roles of secretome and exosomes in the cardiovascular system, both in physiological and pathological conditions, and explore the broad applications of secretome and exosomes in mitigating CVD progression. Secretome and exosomes, which play crucial roles in intercellular communication, tissue repair, and immunomodulation, have shown potential in reducing cardiovascular disease progression by inhibiting inflammation, promoting blood vessel growth, and regulating biological mechanisms. Further research is needed to maximize their use in advanced cardiovascular therapy. © 2025, Indonesian Society of Internal Medicine. All rights reserved.