A potentiometrically tuned-glucose biosensor was fabricated using core-shell nanocomposite based on zinc oxide encapsulated chitosan-graft-poly(vinyl alcohol) (ZnO/CHIT-g-PVAL). In a typical experiment, ZnO/CHIT-g-PVAL core-shell nanocomposite containing <20 nm ZnO nanoparticles was synthesized using wet-chemical method. The glucose responsive bio-electrode, i.e., glucose oxidase/ZnO/chitosan-graft-poly(vinyl alcohol) (GOD/ZnO/CHIT-g-PVAL/ITO) was obtained by immobilization of glucose oxidase (GOD) onto the electrode made of resulting ZnO core-shell nanocomposite coated on the indium-tin oxide (ITO) glass substrate. The ZnO/CHIT-g-PVAL/ITO and GOD/ZnO/CHIT-g-PVAL electrodes were characterized with Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM), whereas ZnO/CHIT-g-PVAL size of core-shell nanoparticles were measured using transmission electron microscopy (TEM). The electrostatic interaction between GOD and ZnO/CHIT-g-PVAL provided the resulting tuned enzyme electrode with a high degree of enzyme immobilization and excellent lifetime stability. The response studies were carried out as a function of glucose concentration with potentiometric measurement. The GOD/ZnO/CHIT-g-PVAL/ITO bioelectrode has showed a linear potential response to the glucose concentration ranging from 2 mu M to 1.2 mM. The glucose biosensor exhibited a fast surface-controlled redox biochemistry with a detection limit of 0.2 mu M, a sensitivity of >0.04 V/mu M and a response time of three sec. ZnO/CHIT-g-PVAL core-shell nanocomposite could be a promising nanomaterials for a range of enzymic biosensors.