Self-powered drug-delivery systems based on conductive polymers (CPs) that eliminate the need for external power sources are of significant interest for use in clinical applications. Osmium redox polymer-mediated glucose/O2 enzymatic biofuel cells (EBFCs) were prepared with an additional CP-drug layer on the cathode. On discharging the EBFCs in the presence of glucose and dioxygen, model drug compounds incorporated in the CP layer were rapidly released with negligible amounts released when the EBFCs were held at open circuit. Controlled and ex situ release of three model compounds, ibuprofen (IBU), fluorescein (FLU), and 4',6-diamidino-2-phenylindole (DAPI), was achieved with this self-powered drug-release system. DAPI released in situ in cell culture media was incorporated into retinal pigment epithelium (RPE) cells. This work demonstrates a proof-of-concept responsive drug-release system that may be used in implantable devices.