Doxorubicin (DOX) is a potent anticancer drug; its use has been limited by its hepatotoxicity, which is due to free radicals generation. This work aims to investigate whether the n-butanol soluble part of the 70% methanol extract of the aerial parts of Moricandia arvensis, alleviates doxorubicin-induced hepatotoxicity. According to the literature data, Moricandia arvensis (Brassicaceae) is renowned for its richness in flavonoid and phenolic acid glycosides. In this work, we have rightly assessed the total phenolic and flavonoid contents of the studied extract (n-butanol extract). The results obtained (TPC: 86.25 ± 0.00 µg GAE/mg; TFC: 22.54 ± 0.01 µg QE/mg) encouraged us to continue our investigations. Wistar albino rats were orally administered with n-butanol extract of M. arvensis (50 mg/kg and 100 mg/kg body weight) or vitamin E as a standard antioxidant (100 mg/kg) for 10 days; and DOX (15 mg/kg on the 8th day that was intraperitoneally injected. At the end of the experiment, blood and liver samples were analyzed for biomarker levels and histopathological changes. Liver homogenates were used to determine oxidative stress parameters such as malondialdehyde (MDA), glutathione peroxidase (GPX) and glutathione (GSH) activity. DOX-administered rats significantly increased different levels of the serum biochemical parameters, increased TBARS level, decreased GPx activity and GSH level in the liver. In addition, M. arvensis (50 mg/kg and100 mg/kg) n-butanol extract treatments significantly decreased the level of TBARS, increased GSH level and GPx activity compared to the DOX-treated rats (p < 0.01). The histological study revealed the hepatoprotective effects of the tested extract on DOX-induced toxicity. This was demonstrated by the preservation of hepatic architecture as well as a reduction in structural and functional changes in the liver. The obtained results indicate a protective action of n-butanol extract of M. arvensis that could be the result of the inhibition of reactive oxygen species (ROS) generation. This may be the result of the presence of phenolic compounds in M. arvensis plant.