Recent breakthroughs in electroactive piezo-biomaterials have driven significant progress towards the development of both, diagnostic and therapeutic purposes, enabling vital sign monitoring, such as heart rate, etc. while also supporting tissue regeneration. Bioelectronic medicine provides a promising method for controlling tissue and organ functions, with 'piezo-electronics' emphasizing the lasting role of electro-active piezo-biomaterials in self-powered devices. This article critically analyses a range of self-powered bioelectronic technologies, including wearable, implantable, regenerative, and cancer therapy applications. Piezoelectric nanogenerators (PENGs) are essential in wearable and implantable systems such as pressure and strain measurements, sensor for human-machine interface, self-powered pacemakers, deep brain stimulation, cochlear implant, tissue restoration and sustained drug delivery, controlled by electrical stimuli from PENGs etc. Regenerative bioelectronics play a key role in healing tissues, such as bone, neural, cardiac, tendon, ligament, skeletal muscle etc. using self-powered implants, which have ability to restore tissue functionality. Additionally, piezoelectric biomaterials are being utilized in cancer treatment, offering more targeted therapies with minimal side effects. Various cancerous tumors can be destroyed by reactive oxygen species (ROS), generated by piezobiomaterials. Data science is also emerging as a crucial tool in optimizing self-powered bioelectronics, enhancing patient outcomes through data-driven strategies, and broadening the role of bioelectronic technologies in modern healthcare.