Diabetic patients are prone to suffer from cardiovascular disease, specifically from ischemic heart disease and diabetic cardiomyopathy, which have a huge impact on morbidity and mortality worldwide. Cardiac fibrosis due to alteration of the extracellular matrix (ECM) remodeling is often observed in diabetes and myocardial fibrosis is an important part of cardiac remodeling that leads to heart failure and death. At single-cell level, the ECM govern, metabolism, motility, orientation, and proliferation. However, in pathological condition such as diabetes, changes in ECM lead to fibrosis and subsequently cardiac stiffness and cardiomyocytes dysfunction. Antidiabetic drugs, particularly sodium-glucose cotransporter-2 (SGLT2) inhibitors have antifibrotic effects and may promote ECM reverse remodeling. In this review, the mechanisms, and the role of ECM remodeling and reverse remodeling as a potential therapeutic target for diabetic cardiomyopathy are discussed.