Type 2 diabetes causes structural and functional changes in the myocardium, which is called cardiomyopathy. Diabetic cardiomyopathy (DCM) is a distinct primary disorder process, independent of coronary artery disease, which leads to heart failure in diabetic patients. Also, DCM is a multifaceted disorder that is one of the leading causes of death in elderly and postmenopausal women. Menopause is associated with decreased and stopped ovarian function, which reduces and stops the production of ovarian hormones, especially estrogen. Moreover, menopause is associated with an increased risk of cardiovascular diseases. Sex steroids such as 17-β estradiol have a variety of protective effects on many tissues in the body, including the cardiovascular system. In this article, the concept of DCM, the underlying molecular signaling pathway, and, finally, the role of 17-β estradiol as one of the most important estrogens in moderating DCM are discussed to provide a theoretical basis for in-depth study.