Cisplatin is a potent anticancer drug, but its clinical application has been limited due to its undesirable physicochemical characteristics and severe side effects. Better drug formulations for cisplatin are highly desired. Herein, we have developed a nanoparticle formulation for cisplatin with high encapsulation efficiency and reduced toxicity by using cisplatin-crosslinked carboxymethyl cellulose (CMC) core nanoparticles made from poly(lactide-co-glycolide)-monomethoxy-poly(polyethylene glycol) copolymers (PLGA-mPEG). The nanoparticles have an average diameter of approximately 80 nm measured by transmission electron microscope (TEM). The encapsulation efficiency of cisplatin in the nanoparticles is up to 72%. Meanwhile, we have also observed a controlled release of cisplatin in a sustained manner and dose-dependent treatment efficacy of cisplatin-loaded nanoparticles against IGROV1-CP cells. Moreover, the median lethal dose (LD(50)) of the cisplatin-loaded nanoparticles was more than 100 mg/kg by intravenous administration, which was much higher than that of free cisplatin. This developed cisplatin-loaded nanoparticle is a promising formulation for the delivery of cisplatin, which will be an effective therapeutic regimen of ovarian cancer without severe side effects and cumulative toxicity.