The use of medicinal plants increased considerably as it is necessary for producing more effective drugs with fewer side effects. Walnut has different properties with therapeutic potential in traditional medicine. The aim of this study is to determine the in vitro antioxidant activity of walnut oil and its cardioprotective effect against doxorubicin induced cardiotoxicity in mice. The in vitro antioxidant activity of the oil was analyzed using ferric reducing antioxidant power (FRAP) and 1,1--diphenyl-β-picrylhydrazyl (DPPH) assay. The FRAP of the oil increases with increase in concentration. The DPPH scavenging activity of the oil increases with increase in concentration but has a low activity when compared with ascorbic acid. Twenty-five mice were divided into five with group A being the control given 0.3ml of 0.9% normal saline; group B was given a cumulative dose of 45 mg/kg body weight of Doxorubicin; group C was given 15 mg/kg body weight of walnut oil only; group D was given 20 mg/kg body weight of walnut oil and cumulative dose of 45 mg/kg body weight of Doxorubicin; and group E was given 10mg/kg body weight of oil and cumulative dose of 45 mg/kg body weight of Doxorubicin. The walnut oil was administered orally daily while Doxorubicin was administered intraperitoneally. At the end of three weeks, the lipid profile was assessed and the histopathological examination of the heart was assessed. In group B, total cholesterol, triglyceride (TG) and high-density lipoprotein (HDL) increases as compared with the control (group A). Group C, D, E showed a decrease in cholesterol and TG. HDL level increased in group C and D while a reduction was noticed in group E. The LDL level of group D and E decreased while that of group C increased. The heart histopathology indicated the toxicity of Doxorubicin as seen in group B however, the toxicity level reduced in group D and E showing moderate multiple foci of myofiber coagulation. There were no observable changes in the heart morphology of group C animal when compared to group A. It can be concluded from our results that walnut oil can be used to reduce toxicity level of Doxorubicin and hence possessed a cardioprotective role.