Implantable biomedical devices (IBDs) have garnered wide-scale attention in recent years due to their enormous contribution to the biomedical sector. However, an uninterrupted and reliable power source has consistently been the primary barrier for IBDs, which is greatly alleviated by batteries. The widespread application of battery-powered IBDs is hindered by several limitations, including bulkiness, limited capacity, shelf-life, and expenditure associated with surgery-based battery recharge/replacement. To address these challenges, state-of-the-art self-powering technologies have emerged, including implantable piezoelectric nanogenerators (iPENGs) and implantable triboelectric nanogenerators (iTENGs). These technologies enable IBDs to operate autonomously by harnessing the minute mechanical movements of internal organs, such as heartbeat, respiration, blood circulation, muscle contraction/relaxation, and lung vibration. This review focuses on the recent advancements in iTENGs and iPENGs for the development of self-powered IBDs with a wide range of applications, including energy harvesting from biomechanical and ultrasound sources and energy storage using batteries and capacitors. This study also explores the extensive sensing applications of IBDs in various areas including cardiac, gastrointestinal, bladder, and ligament-strain monitoring. Finally, therapeutic applications of IBDs, such as nerve stimulation, bone stimulation, cartilage therapy, tissue regeneration, muscle stimulation, drug delivery, and diabetes management are discussed.