Activated transcription factor 6 (ATF6) is a transmembrane glycoprotein located in the endoplasmic reticulum.It exists widely in various tissues including myocardium and participates in endoplasmic reticulum stress (ERS) by regulating the unfolded protein response (UPR) signal pathway, which has become one of the major regulators of organs/tissues homeostasis and is of great significance in signal transduction, gene expression and protein synthesis. A number of studies have shown that ATF6 plays an important regulatory role in the occurrence and development of atherosclerosis, myocardial infarction, cardiac hypertrophy, diabetic cardiomyopathy, arrhythmia and other common cardiovascular diseases (CVD). At present, some studies have proved that ATF6 can regulate its activity and function to intervene the occurrence and development of some CVD. As a result, whether a small molecule regulator can be designed to treat some CVD by regulating ATF6 has become a research hot-spot. ATF6-based therapies have made great progress and have shown promising efficacy in small animal models of CVD and other systemic protein-based diseases. The small molecule regulator to ATF6 has a broad application prospect in cardiovascular disease, but further basic and clinical studies are still needed to lay the theoretical and practical foundation for its application. In present paper, the structure, classification and correlation of ATF6 with CVD are reviewed in order to provide references for experimental researches, clinical diagnoses and treatments of CVD.