Asteriscus graveolens (Asteraceae) is a medicinal herb, used in Algeria to treat diabetes, hypertension, pain, fever, inflammation and gastrointestinal diseases. Doxorubicin (DOX) is an antibiotic antineoplastic drug used to treat many types of cancers; unfortunately, its antitumor activity links toxic effects to several organs including the heart, liver and testis. The appropriate mechanism of its organotoxicity is linked to free reactive oxygen species (ROS) generation and oxidative stress induction. In this study, the antioxidant and protective role of A. graveolens and vitamin E (Vit E) against DOX-induced hepatic and testicular toxicity was assessed. Thirty-five rats were distributed equally into five groups and orally administered with n -butanol extract of A. graveolens (75 mg/kg bw) or Vit E (100 mg/kg bw) for 10 days in the absence or presence of a single intraperitoneal injection of DOX (15 mg/kg bw). The results revealed that DOX toxicity induced a significant elevation in the liver serum marker enzymes and lipid profile levels (cholesterol, triglycerides and LDL). In addition, DOX-induced hepatic and testicular oxidative injury was indicated due to a significant increase of malondialdehyde levels along with a noticeable reduction of the antioxidant system. A. graveolens and Vit E treatment might improve the biochemical and histopathological changes induced by DOX. A. graveolens has antioxidant and hypolipidemic properties and it can reduce DOX-induced oxidative damage in the liver and testis. A. graveolens showed a similar protective effect of Vit E against DOX damage due to the presence of an abundant amount of phenolics such as flavonoids. This protection is mediated by their direct free-radical scavenging activity and their ability to prevent DOX depletion of the hepato-testicular antioxidant defense systems.