In this report, a novel type of a hollow CuO polyhedron-modified electrode for sensitive nonenzymatic glucose detection has been fabricated by a templating approach. The morphologies and structures were characterized by field-emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Raman spectrum and X-ray photoelectron spectroscopy (XPS). These results show that the as-prepared hollow CuO consists of numerous CuO nanoplates. The electrochemical performance for glucose detection was investigated by cyclic voltammetry and chronoamperometry. The hollow CuO polyhedron-modified electrode exhibits a high sensitivity of 1112 μA mM⁻¹ cm⁻² with a detection limit of 0.33 μM (S/N = 3) at +0.55 V, and the linear range is up to 4 mM. Moreover, the hollow CuO polyhedron-modified electrode is highly resistant to the interference from interfering species such as sodium chloride (NaCl), ascorbic acid (AA) and uric acid (UA). The hollow CuO polyhedron-modified electrode exhibits high sensitivity, low detection limit, good stability and fast response towards the oxidation of glucose; thus, it may be a promising nonenzymatic glucose sensor.