Integrating biomedical electronic devices holds profound promise for advancements in healthcare and enhancing individuals' quality of life. However, the persistent challenges associated with the traditional batteries' limited lifespan and bulkiness hinder these devices' long-term functionality and consistent power supply. Here, we delve into the biology and material interfaces in self-powered medical devices by summarizing the intrinsic electric demands in humans, analyzing material and biological mechanisms for electricity generation and storage, and discussing the pathways toward self-chargeable powering. As a result, the current challenges in material designs and biological integrations emerged to shape the future directions in advancing self-powered medical devices. This paper calls on the community to integrate biology and material science to develop self-powering medical devices and improve their clinical prospects.