A self-powered, piezotronic effect-enhanced glucose sensor based on metal-semiconductor-metal (M-S-M) structured single ZnO nanowire device is demonstrated. A triboelectrical nanogenerator (TENG) is integrated to build a self-powered glucose monitoring system (GMS) to realize the continuously monitoring of glucose concentrations. The performance of the glucose sensor is generally enhanced by the piezotronic effect when applying a -0.79% compressive strain on the device, and magnitude of the output signal is increased by more than 200%; the sensing resolution and sensitivity of sensors are improved by more than 200% and 300%, respectively. A theoretical model using energy band diagram is proposed to explain the observed results. This work demonstrates a promising approach to raise the sensitivity, improve the sensing resolution, and generally enhance the performance of glucose sensors, also providing a possible way to build up a self-powered GMS.