This study aimed to present a new heart of P. dactylifera (HP) extract loaded chitosan nanoparticles and estimate its anticancer, antimicrobial, antioxidant activity and free radical scavenger effect (in vitro). This nano-supplement may prevent doxorubicin cardiotoxicity and nephrotoxicity in rat model. The HP extract was loaded on chitosan nanoparticles producing HP-ChNPs, then characterized. The antioxidant properties of the HP-ChNPs was assessed in vitro. The antibacterial activity against three-gram positive bacteria and two gram-negative bacteria were done. The in vitro studies of cytotoxicity against MCF7, CaCo3, and Hela cell lines were also evaluated. Then, the protective effect of the HP-ChNPs (2 mg/kg, IP) was evaluated against doxorubicin induce organ toxicity in a rat model. The in vitro studies revealed the antibacterial, anticancer and antioxidant activities of the HP-ChNPs. The in vivo study demonstrates reduction of heart and kidney apoptosis with increased programmed cell death protein-1 (PD-1); as the major anticancer drug (doxorubicin) pathway is to release free radicals with decreased PD-1 levels and induction of apoptosis. In conclusion, the HP-ChNPs, in a very small dose, might be a promising supplement to avoid doxorubicin toxicity with improvment the antioxidant enzymes without affecting its anticancer activity.