The present study reports, for the first time, the development and use of core-shell amino-terminated chitosan (Cs) hyperbranched nanoparticles (HBCs-NH2 NPs) as a novel natural polymer-based electrode modifier for efficient electrochemical systems. The electrochemical activity of the developed HBCs-NH2 NPs as compared to Cs NPs was identified by standard oxidation-reduction reactions of ferricyanide. The oxidation-reduction peaks height was about twofold higher than the response of Cs-modified electrode. On the other hand, NADH oxidation at the nanostructured surfaces confirmed the electrocatalytic activity where the oxidation of NADH appeared at a lower overpotential (from 805mV to 635mV vs Ag/AgCl). Eventually, a diffusion-controlled process was confirmed from the scan rate effect.