Doxorubicin (DOX) is one of the most widely used chemotherapy agents which is associated with several adverse effects on heart tissue including cardiomyopathy. Curcumin (Cur), a well-known dietary polyphenol could exert important cardioprotective effect but its biological application is limited by chemical insolubility. In order to overcome this problem in this study, we synthesized gold nanoparticles completely based on curcumin (Cur-AuNPs). This nanoparticle, on the one hand, could bring out a stable delivery way for curcumin that cause more solubility and on the other hand, will cause more efficacy. UV-Visible, size, surface charge, TEM and FTIR characterization also in-vitro cytotoxicity effect on H9C2 cells were performed for Cur-AuNPs. Biological efficacy of Cur-AuNPs was evaluated after acute cardiotoxicity induction in Balb/c with DOX injection in comparison to carrier-free curcumin. Heart protective effect of Cur-AuNPs was evaluated 24 h after toxicity induction by quantifying serum biomarkers, myocardial histological changes and cardiomyocyte apoptosis. Long term Cur-AuNPs protective effect was evaluated for heart/body weight changes and myocardial fibrosis after 14 days of toxicity induction. The results revealed that Cur-AuNPs delivery system was capable to apply heart protection in a much more effective way than curcumin. Cur-AuNPs efficacy is evident both in the short-term results, 24 h after toxicity induction, by reduction of serum biomarkers and apoptotic proteins (Bax and Caspase-3) and no sign of interfibrillar haemorrhage, and intercellular spaces in microscopic images also in the long-term study,14 days later, that indicate Cur-AuNPs could successfully prevent body and heart weight loss.