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The emergence of human-motion-based energy harvesters is a reflection of the need to develop future energy supplies for small-scale human-motion-based self-powered and self-sensing devices. Such systems have a widespread application in modern society, which includes health monitoring, medical care, wearable devices, wireless sensor nodes, and outdoor rescue. This paper overviews the state-of-the-art and recent progress in human-motion-based self-powered and self-sensing devices, where we classify the range of available energy sources, the energy conversion mechanisms, relevant materials, and novel device architectures to harvest human-motion energy. The range of human-motion energy sources is classified into three categories based on how they act as excitation sources for energy harvesting. The commonly used energy conversion mechanisms are then overviewed in detail, which include electromagnetic, piezoelectric, and electrostatic (dielectric elastomer generator and triboelectric nanogenerator) mechanisms, and the range of potential electroactive materials is discussed. In addition, the harvesting structures, operating mechanisms, and performance of human-motion-based energy harvesters are overviewed, discussed, and characterized based on the range of available human-motion energy sources. Furthermore, the application of self-powered devices in delivering power to implantable medical devices, wearable devices, and other low-powered electronics are comprehensively reviewed. The state-of-the-art and future advances in human-motion-based self-sensing devices are then reviewed and related to their application in human activity recognition, health monitoring, and human–machine interactions. Finally, key developments are summarized and discussed, and the potential research directions and critical challenges are presented to highlight future opportunities.