A direct electrocatalytic activity of glucose oxidation on cuprous oxide modified glassy carbon electrode is reported. Cu2O nanocubes were synthesized by a simple wet chemical route in the absence of surfactants. Purity, shape and morphology of Cu2O are characterized by XRD, SEM, XPS and DRS-UV. The Cu2O nanocubes-modified glassy carbon electrode (GCE) exhibited high electrocatalytic activity towards glucose oxidation compared with bare GCE electrode. At an applied potential of +0.60 V, the Cu2O electrode presented a high sensitivity of 121.7 μA/mM. A linear response was obtained from 0 to 500 μM, a response time less than 5 s and a detection limit of 38 μM (signal/noise=3). The Cu2O nanocubes modified electrode was stable towards interfering molecules like uric acid (UA), ascorbic acid (AA) and dopamine (DA). In short, a facile chemical preparation process of cuprous oxide nanocubes, and the fabricated modified electrode allow highly sensitive, selective, and fast amperometric sensing of glucose, which is promising for the future development of non-enzymatic glucose sensors.