Compared with the DCM group, EAEPOL treatment significantly lowered random blood glucose levels in a time-dependent manner, improved cardiac function, reduced fibrosis, enhanced antioxidant capacity, modulated Nrf2/HO-1 signaling, and restored endothelial/fibrotic marker expression (<i>P</i> < 0.05, <i>P</i> < 0.01, <i>P</i> < 0.001 or <i>P</i> < 0.0001).<h4>Conclusion</h4>EAEPOL exerts significant protective effects against DCM via reducing hyperglycemia, Nrf2/HO-1-mediated antioxidant responses and suppression of myocardial fibrotic remodeling. The gene discussed is NFE2L2; the disease is familial dilated cardiomyopathy.