Doxorubicin (DOX) is a chemotherapeutic drug with a broad spectrum of antineoplastic effects against several malignancies. Nonetheless, its clinical utility is limited due to its dose-dependent chronic cardiotoxicity, myelosuppression, and hepatotoxicity. Virgin coconut oil (VCO) consumption is associated with numerous biological and pharmaceutical impacts. The goal of the current study was to assess the protective effects of VCO against doxorubicin-induced hepatotoxicity. Four groups of rats were assigned: control, DOX (15 mg/kg, single dose intraperitoneally), VCO (10 ml/kg, orally for 7 days), and VCO+DOX. Rats given DOX experienced significant rises in ALT and AST serum levels as well as a decrease in albumin levels. Additionally, a significant elevation in MDA level was accompanied by a significant reduction in GSH, CAT, and SOD in the liver tissue following DOX exposure. Moreover, the levels of pro-inflammatory (NF-κB, TNF-α, and IL-6) and pro-apoptotic (caspase-3) markers were significantly increased, while the anti-apoptotic marker (Bcl-2) was significantly decreased. On the other hand, the pretreatment with VCO significantly reduced the level of MDA, caspase-3, and liver function markers and enhanced the antioxidative molecule in response to DOX injection. However, VCO supplementation failed to inhibit the inflammatory response in the liver tissue following DOX exposure which may be due to its high saturated fatty acids content.