A high-performance non-enzymatic glucose sensor based on hybrid metal-oxides is proposed. Dumbbell-shaped double-shelled hollow nanoporous CuO/ZnO microstructures (CuO/ZnO-DSDSHNM) were prepared via the hydrothermal method using pluronic F-127 as a surfactant. This structure is studied by various physicochemical characterizations such as scanning electron microscopy, X-ray diffraction spectroscopy, inductively coupled plasma atomic emission spectroscopy, elemental mapping techniques, X-ray photoelectron spectroscopy, and transmission electron microscopy. This unique CuO/ZnO-DSDSHNM provides both a large surface area and an easy penetrable structure facilitating improved electrochemical reactivity toward glucose oxidation. The prepared CuO/ZnO-DSDSHNM was used over the glassy carbon electrode (GCE) as the active material for glucose detection and then coated by Nafion to provide the proposed Nafion/CuO/ZnO-DSDSHNM/GCE. The fabricated glucose sensor exhibits an extremely wide dynamic range from 500 nM to 100 mM, a sensitivity of 1536.80 µA mM-1 cm-2, a low limit of detection of 357.5 nM, and a short response time of 1.60 s. The proposed sensor also showed long-term stability, good reproducibility, favorable repeatability, excellent selectivity, and satisfactory applicability for glucose detection in human serum samples. The achieved high-performance glucose sensing based on Nafion/CuO/ZnO-DSDSHNM/GCE shows that both the material synthesis and the sensor fabrication methods have been promising and they can be used in future researches.