Microelectronics, as indispensable tools in clinics, can monitor physiological signals, treat diseases, and promote human health. An efficient and uninterrupted energy supply is key to the application of implanted and wearable devices. Traditional energy supply systems typically rely on batteries and connections to external power sources; however, the inconvenience of charging, limited working life of the battery, and the risk of reoperation limit their applications, and meanwhile prompt investigation of self-driven, long-term power supplies. The nanogenerator, as an ideal power supply, collects biomechanical energy from physiological activities such as muscle movement, heartbeat, respiration, gastric peristalsis, and performs electrical signal conversion for detection of physiological/pathological indicators, cardiac pacing, nerve stimulation, tissue repair, and weight control. Here, we review the design of nanogenerators and their biomedical applications, which may inspire future development of self-powered medical devices. The nanogenerator, as an ideal power supply, collects biomechanical energy from physiological activities such as muscle movement, heartbeat, respiration, gastric peristalsis, and performs electrical signal conversion for detection of physiological/pathological indicators, cardiac pacing, nerve stimulation, tissue repair, and weight control. A summary of the biomedical applications of nanogenerators will inspire future development of self-powered medical equipment. • The biomedical applications of nanogenerator-based devices are systematically summarized. • The design and working principle of nanogenerators driving implantable/wearable devices are comprehensively reviewed. • Nanogenerators can collect and transform biomechanical energy, and are expected to be more widely used in life monitoring and regulation.