Background: This study evaluated the cardioprotective effect of Ajwa nano-preparation against doxorubicin-associated cardiotoxicity. Methods: Twenty-four male Wistar rats (200-250 g) were divided into 3 groups. One group was given the nanopreparation containing both Ajwa fruit and pit in a dose of 1.4 g/kg orally 1 hour before doxorubicin infusion (Dates-DOX group). Another group was given the vehicle for 1 hour before doxorubicin infusion (DOX group). The third group received the vehicle but no DOX infusion (time control). Cardiac hemodynamics, blood pressure, cardiac contractility, and conductivity were recorded before and after 45 minutes of infusion of doxorubicin (15 mg/kg, slow intravenous over 45 minutes). Blood samples were collected before and after doxorubicin infusion. Heart tissue samples were collected and snap frozen until assay of reduced glutathione. Results: Rats pre-administered Ajwa nanopreparation were protected from doxorubicin-associated systolic and diastolic dysfunction based on the significant elevation in the rate of rise in left ventricular pressure (dp/dt(max)) and (dp/dt(min)) compared with the DOX group. In addition, it prevented the doxorubicin-associated ischemia based on the significant shortening in QT interval, JT interval, and T-peak-T-end interval versus the DOX group. There was no effect on atrial conductivity (PR interval and P duration). Ajwa pretreatment increased the antioxidant capacity of cardiac tissue, as evidenced by increasing the cardiac content of reduced glutathione compared with the untreated doxorubicin group. Conclusion: Ajwa nanopreparation protects from doxorubicin-associated cardiotoxicity through alleviating cardiac ischemia and increasing cardiac antioxidant capacity.