Myocardial infarction (MI) is the most common cardiovascular disease (CVD) and the leading cause of mortality worldwide. Recent advancements have identified human endometrial mesenchymal stem cells (hEnMSCs) as a promising candidate for heart regeneration, however, challenges associated with cell-based therapies have shifted focus toward cell-free treatments (CFTs), such as exosome therapy, which show considerable promise for myocardial tissue regeneration. MI was induced in male Wistar rats by occluding the left anterior descending (LAD) coronary artery. The hEnMSCs-derived exosomes (hEnMSCs-EXOs) were encapsulated in injectable fibrin gel inside the cardiac tissue. The encapsulated hEnMSC-EXOs were administered, and their effects on myocardial regeneration, angiogenesis, and heart function were monitored for 30 days post-MI. The treatments were evaluated through histological analysis, echocardiographic parameters of left ventricular internal dimension at end-diastole (LVIDD) and end-systole (LVID), left ventricular end-diastole volume (LVEDV), left ventricular end-systole volume (LVESV), and left ventricular ejection fraction (LVEF) and molecular studies. Histological findings demonstrated significant fibrosis and left ventricular remodeling following MI. Treatment with fibrin gel-encapsulated hEnMSCs-EXOs substantially reduced fibrosis, enhanced angiogenesis, and prevented heart remodeling, leading to improved cardiac function. Notably, 30 days after encapsulated hEnMSCs-EXOs were delivered corresponded with a less inflammatory microenvironment, supporting cardiomyocyte retention in ischemic tissue. This study highlights the potential of encapsulated hEnMSCs-EXOs in fibrin gel as a novel therapeutic strategy for ischemic myocardium repair post-MI. The findings underscore the importance of biomaterials in advancing stem cell-based therapies and lay a foundation for clinical applications to mitigate heart injury following MI.