Adriamycin is a widely used and effective antitumor drug; however, its application is limited by various side effects, including irreversible cardiotoxicity. The central role of cardiac atrophy in Adriamycin-induced cardiotoxicity has been revealed; however, the underlying mechanism of this process remains unclear. Artemether is a well-known Chinese herbal medicine, and its pharmacological action is related to the regulation of mitochondrial function and redox status. The present study determined the effects of artemether on Adriamycin-induced cardiotoxicity and investigated the underlying mechanisms. After mouse model establishment and artemether intervention, experimental methods including pathological staining, immunohistochemistry, immunofluorescence, immunoblotting, ELISA and reverse transcription-quantitative PCR were used to evaluate the therapeutic effect. The results demonstrated that artemether prevented Adriamycin-induced cardiac atrophy and recovered the intercombination of connexin 43 and N-cadherin at the intercalated discs. Artemether also regulated the autophagy pathway and restored the unbalanced ratio of Bax and Bcl-2 in myocardial cells. In addition, the increased serum H2O2 levels after Adriamycin exposure were significantly decreased by artemether, and the mitochondrial alterations and redox imbalance in myocardial cells were also improved to varying degrees. In summary, the findings of the present study provide reliable evidence that artemether could ameliorate cardiac atrophy induced by Adriamycin. This therapeutic approach may be translated to the clinic for preventing drug-induced heart diseases.