Cardiotoxicity and nephrotoxicity due to the abnormal production of free radicals have been observed in patients treated with the anticancer antibiotic adriamycin (ADR). The aim of the present study was to evaluate the role of the heart of palm extract in preventing oxidative stress, cardiotoxicity and nephrotoxicity induced by ADR. In this work, an aqueous ethanolic extract of the heart of the Phoenix dactylifera tree (HP) was investigated. The polyphenol content was evaluated by gas chromatography-mass spectrometry (GC-MS) and High-performance liquid chromatography (HPLC). The protective effect of the HP-extract (250 and 500 mg/kg, p.o.) was evaluated along with ADR administration (cumulative dose 15 mg/kg, IP) in rats. The HP-extract (500 mg/kg) treated group showed significant reductions in cardiotoxicity and nephrotoxicity serum markers, apoptotic percentage, and caspase-3 and cyclooxygenase-2 level, with an improvement in antioxidant enzymes in both heart and kidney homogenate, compared with the ADR-induction group. The cardiac and kidney programmed cell death protein-1 (PD-1) was increased in high dose HP-extract treated rats after being inhibited by ADR administration. In conclusion, the HP-extract might be a promising food supplement for preventing the cardiotoxicity and nephrotoxicity induced by ADR administration.