The study aimed to investigate the protective effect of grape seed extract (GSE) and L-carnitine (L-CA) in reducing toxicity caused by doxorubicin (DOX) in rats. Six groups of male albino rats were used in the experiment. Group I: The Control group received a normal saline solution throughout the 35-day experimental period. Group II: Given GSE (100 mg/kg b.wt., daily). Group III: Given L-CA (150 mg/kg b.wt., twice a week). Group IV: Administered DOX (10 mg/kg b.wt.) on day 28 of the experiment to induce toxicity. Group V: Received a combination of GSE (100 mg/kg b.wt.) and DOX (10 mg/kg b.wt., on day 28). Group VI: Received a combination of L-CA (150 mg/kg b.wt.)  and DOX (10 mg/kg b.wt., on day 28). The results showed that the rats injected with DOX had reduced body weight, as well as signs of microcytic hypochromic anemia, leukopenia, neutropenia, lymphopenia, monocytopenia, and thrombocytopenia. However, the groups pretreated with GSE and L-CA showed improvement in these parameters compared to the DOX group. This suggested that GSE and L-CA have a protective effect against DOX-induced toxicity.