Detecting and manipulating disease-related bioactive molecules in a controlled way is crucial to elucidate the mechanisms of disease and develop effective diagnostics and therapeutics. Enzymatic biofuel cells (EBFCs) are a kind of fuel cell that rely on enzymes as biocatalysts to convert the chemical energy derived from biosourced fuels into electrical energy. This feature enables EBFCs to be used as self-powered biosensors (SPBs) for biological analysis. This review summarizes the latest research progress in EBFCs in terms of working principles, electron transfer mechanisms, and enzyme immobilization strategies. In addition, it emphasizes applications including disease diagnosis, precision therapy, and theranostic integration. Finally, challenges and opportunities for clinical translation in this field are discussed. By overcoming technical and biological limitations, EBFCs have the potential to revolutionize biomedical diagnostics and therapeutic monitoring, thus fostering the development of efficient and autonomous implantable biosensors.



