Hierarchical core-shell IrO2@NiO nanowires (NWs) have been designed through two simple steps, which combined electrospinning of IrO2 conductive core and chemical bath deposition growth of ultracontinuous NiO nanoflakes. Scanning electron microscopy, transmission electron microscopy, X-ray diffraction, energy-dispersive X-ray spectrometry mapping, and X-ray photoelectron spectroscopy were employed to characterize the morphologies and structures of the as-prepared samples, and the results were also carefully compared with that of pure NiO nanoflowers and IrO2 NWs. Electrochemical studies indicate that the as-prepared core-shell IrO2@NiO NWs exhibited excellent nonenzymatic detection ability to glucose. At 0.35 V, it offered a sensitivity of 1439.4 μA mM-1 cm-2 (one order higher than pure NiO) with a wider linear range from 0.5 μM to 2.5 mM, a low detection limit of 0.31 μM (signal-to-noise ratio = 3, and moreover, good resolution in low glucose concentration, reproducibility, and long-term performance stability. Owing to the high sensitivity and performance, application of the proposed sensor in monitoring saliva glucose was also demonstrated; the results indicated that the sensor can effectively distinguish the diabetes from the healthy people and even the varying degrees of diabetic.