In this study, we found that miR-503 is involved in the progress of DCM, and Phase II enzyme inducer (CPDT) could reverse the impaired structure and function, reduce myocardial apoptosis, relieve the occurrence and development of DCM through miR-503 and Nrf2/ARE signaling pathway, and provide new therapeutic targets for DCM. Here, NFE2L2 is linked to familial dilated cardiomyopathy.