Designing highly active material to fabricate a high-performance noninvasive wearable glucose sensor was of great importance for diabetes monitoring. In this work, we developed CuxO nanoflakes (NFs)/Cu nanoparticles (NPs) nanocomposites to serve as the sensing materials for noninvasive sweat-based wearable glucose sensors. We involve CuCl2 to enhance the oxidation of Cu NPs to generate Cu2O/CuO NFs on the surface. Due to more active sites endowed by the CuxO NFs, the as-prepared sample exhibited high sensitivity (779 μA mM−1 cm−2) for noninvasive wearable sweat sensing. Combined with a low detection limit (79.1 nM), high selectivity and the durability of bending and twisting, the CuxO NFs/Cu NPs-based sensor can detect the glucose level change of sweat in daily life. Such a high-performance wearable sensor fabricated by a convenient method provides a facile way to design copper oxide nanomaterials for noninvasive wearable glucose sensors.