<p>Although doxorubicin (DOX) chemotherapy is widely used to treat malignant tumors, its cardiotoxicity restricts its widespread use. Flavonoids may mitigate DOX-induced cardiotoxicity. A systematic review was conducted to determine whether flavonoids can prevent DOX-induced cardiotoxicity. Therefore, it would be interesting to examine the effects of flavonoids on DOX activity. Based on a Boolean query in the well-known Scopus database, we present our review of doxorubicin and flavonoids simultaneously as combination drugs for cancer treatment. Following the retrieval and review of the intended investigations based on the input keywords, the anticancer mechanisms of flavonoids and doxorubicin are discussed, along with their effects on different targets. Several apoptotic/pro-apoptotic proteins are induced through targeted signaling pathways, which may activate several caspases that cause apoptosis, leading to cell death. In this study, flavonoids differentially modulated the efficacy of doxorubicin chemotherapeutics by interfering with chemotherapy-induced apoptosis and cell cycle arrest. Based on this information, we were able to better understand how dietary agents may affect chemotherapy.</p>