Autophagy has been extensively studied in a variety of pathologies, including neurological disorders, cancers, muscle diseases, aging, and cardiovascular diseases. Doxorubicin (Dox) is a potent anticancer drug widely used to treat various cancers. Despite its therapeutic benefits, it has cardiotoxic side effects, interfering with its clinical application. Dox-induced cardiomyopathy (DIC) is one of the most prominent and lethal side effects associated with the use of Dox. Numerous investigations have revealed that Dox administration impacts autophagy; however, the precise mechanism by which Dox modifies this process remains unclear, as the role of autophagy in heart tissue is controversial, ranging from being cytoprotective to cytotoxic. Various therapeutic interventions, including pharmacological drugs and natural products, have been reported to influence the autophagic flux in DIC. In this review, we explore the therapeutic potential of autophagy modulation in DIC, focusing on how various pharmacological drugs and natural products influence autophagy to mitigate cardiac damage. This review uniquely emphasizes the mechanistic role of autophagy in DIC and provides a comprehensive analysis of therapeutic interventions targeting autophagy as a strategy for cardioprotection.