The current study evaluated the protective effect of bioactive compounds in avocado peels as a by-product against doxorubicin toxicity in rats. Twenty four male rats divided into two main groups: The first group (6 rats) fed basal diet and served as negative control. The second group (18 rats) received doxorubicin (15 mg/kg i.p.) on the 28th day to induce toxicity. The second group was divided into 3 subgroups as follows: Group (1): fed basal diet only (and served as a positive control). Group (2): fed on basal diet + (2.5%) of dried avocado peels. Group (3): fed on basal diet + (5%) of dried avocado peels. At the end of the experiment, biological data were calculated, blood samples were taken, heart tissue was collected and weighted. Serum was separated to biochemical analysis. Tissue lipid peroxidation and activity of antioxidant enzymes in heart were also performed. Heart functions and lipid profile were determined in serum. The obtained results revealed that doxorubicin caused a significant elevation in (MDA, CK-MB, CPK, CTNI and LDH) whereas reduced the biological parameters and antioxidants (SOD, CAT, GPx) levels. On the other hand administration of avocado peels improved heart functions and levels of cardiac antioxidant enzymes. Furthermore, histopathological examination of heart tissue confirmed these findings. Avocado peels can be used as a potent preventive agent against doxorubicin toxicity in rats.