Self-powered materials, including piezoelectric, pyroelectric, and photoelectric materials, have been playing a critical role due to their excellent physical features responsive to external pressure, thermal and photo-stimuli to generate an intrinsic electric field for self-powered motivation or follow-up molecular medical catalysis for an efficient cell apoptosis or lesion treatment efficacy. This chapter aims to discuss the fundamentals, categories, constructions, and mechanisms of various self-powered materials, and furthermore elucidate their versatile biomedical applications such as biocatalysis, cell elimination, tumor therapy, bioelectric devices, contaminant degradation, etc.