Chitosan is a biocompatible natural polysaccharide, which has been employed as a polymeric scaffold for versatile, systemic delivery platforms and for locally injectable gels with temperature-sensitive viscosity modulation. Despite the extensive investigation on the chemical modification strategies, however, most of the chitosan-based delivery platforms have been focused on the encapsulation of hydrophobic drugs, which can be simply adsorbed on the chitosan scaffolds by hydrophobic interaction via the postparticle-formation drug-loading process. Herein, we present the facile formation of a cisplatin-coordinated chitosan nanoplatform by exploiting the divalent metal (Pt-II)mediated conformational changes of chitosan chains, which allows for the simultaneous drug-loading and nanoparticle formation. To this end, the native chitosan has been chemically modified with short polyethylene glycol and malonic acid as a colloidal stabilizer and a bidentate chelating ligand for PtIl coordination, respectively. The resulting Pe-modified polyampholytic chitosan (Pt-II-MPC) has been self-associated in aqueous media by hydrophobic segregation into a compact nanostructure, which exhibited an attenuated viscosity and pH-sensitive release of Pt-II compounds. Once the cationic drug molecules have been released under mild acidic conditions, the neutralized Pt-II-free MPC undergoes interchain flocculation near the isoelectric point because of the polyampholytic property, possibly allowing for the facilitated endosomal escape during the cellular endocytosis by the known membrane perturbation property of chitosan.