Docetaxel (DOC), an antimicrotubule, is used to inhibit the proliferation of various kinds of cancer cells. However, it has serious adverse side effects that restrict its clinical application. The aim of the present study was to examine the antitumor activity of the DOC-loaded nanoemulsions based on orange oil (DOC-NEOO) and to assess its cardiotoxicity in mice bearing Ehrlich tumor in their ascetic fluid (EAC). One hundred twenty female Swiss Albino mice were divided into six groups (n=20). Groups I and II were the untreated mice (Control (-)) and the mice administered orally with 0.1ml of NEOO (NEOO (-)), respectively. Group III was the mice bearing EAC that served as the control (+). Groups IV-VI were mice bearing EAC treated with 0.1ml of DOC-NEOO, NEOO and DOC-water, respectively. The mean survival times of both of DOC-NEOO and NEOO (+) groups have enhanced, while the tumor volumes in their ascetic fluid have decreased when compared to the DOC-water group. The administrations of the formulas incorporating NEOO into the mice have enhanced the amount of high density lipoproteins and reduced the amount of cholesterol and triglyceride in their serum. They have also improved the antioxidant activities of glutathione peroxidase and superoxide dismutase in the heart tissues of the mice. Additionally, they decreased the creatine kinase in serum. In conclusion, incorporating the DOC into the NEOO has enhanced its efficacy and reduced its effect on the heart.