The paper deals with theoretical and experimental studies for the development of a self-powered structural health monitoring (SHM) system using macro-fiber composite (MFC) patches. The basic idea is to integrate the actuation, sensing, and energy harvesting capabilities of the MFC patches in a SHM system operating in different regimes. As an example, during flight, under the effects of normal structural vibrations, the patches can work as energy harvesters by maintaining or restoring the battery charge of the stand-by SHM electronic board; on the other hand, if relevant/abnormal loadings are applied, or if local faults produce a noticeable stiffness variation of the monitored component, the patches can act as sensors for the power-up SHM board. During maintenance, the patches can then work as actuators, to stress the structure with pre-defined load profiles, as well as sensors, to monitor the structural response. In this paper, the investigation, based on the electromechanical impedance technique, is carried out on a system prototype made of a cantilevered composite laminate with six MFC patches. A high-fidelity nonlinear model of the system, including the piezoelectric hysteresis of the patches and three vibration modes of the laminate beam, is presented and validated with experiments. The results support the potential feasibility of the system, pointing out that the energy storage can be used for recharging a 3V-65mAh Li-ion battery, suitable for low-power electronic boards. The model is finally used to characterize a condition-monitoring algorithm in terms of false alarms rejection and vulnerability to dormant faults, by simulating built-in tests to be performed during maintenance.