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This paper presents a facile method to fabricate nanostructured copper-oxide (Cu2O/CuO) electrodes with columnar morphology for non-enzymatic glucose sensing. The electrodes were fabricated using a two-step method; first by producing Cu nanostructures through glancing angle deposition (GLAD), followed by a thermal annealing process at various temperatures. The nanostructures were characterized by X-ray diffraction and scanning electron microscopy to evaluate their structural and morphological properties. The optical properties of the electrodes were also investigated by VIS/NIR spectroscopy. Electrochemical characterization revealed that Cu2O outperformed other copper-based nanostructures, with the best sensitivity of 1394 μAcm-2 mM-1 and the lowest limit of detection (LOD) of 0.052 μM. The superior sensor also exhibits two broad linear ranges of 0.01–2 mM and 2–5 mM at the optimized potential of 0.6 V. The Cu2O electrodes demonstrate the merits of reproducibility, selectivity, fast response time, and high accuracy in measuring glucose levels in real blood serum samples.