Harnessing electrochemical energy in an engineered electrical circuit from biochemical substrates in the human body using biofuel cells is gaining increasing research attention in the current decade due to the wide range of biomedical possibilities it creates for electronic devices. In this report, we describe and characterize the construction of just such an enzymatic biofuel cell (EBFC). It is simple, mediator-free, and glucose-powered, employing only biocompatible materials. A novel feature is the two-dimensional mesoporous thermally reduced graphene oxide (rGO) host electrode. An additionally novelty is that we explored the potential of using biocompatible, low-cost filter paper (FP) instead of carbon paper, a conductive polymer, or gold as support for the host electrode. Using glucose (C 6 H 12 O 6 ) and molecular oxygen (O 2 ) as the power-generating fuel, the cell consists of a pair of bioelectrodes incorporating immobilized enzymes, the bioanode modified by rGO−glucose oxidase (GOx/rGO), and the biocathode modified by rGO−laccase (Lac/rGO). Scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/ EDX), transmission electron microscopy, and Raman spectroscopy techniques have been employed to investigate the surface morphology, defects, and chemical structure of rGO, GOx/rGO, and Lac/rGO. N 2 sorption, SEM/EDX, and powder X-ray diffraction revealed a high Brunauer−Emmett−Teller surface area (179 m 2 g −1 ) mesoporous rGO structure with the high C/O ratio of 80:1 as well. Results from the Fourier transform infrared spectroscopy, UV−visible spectroscopy, and electrochemical impedance spectroscopy studies indicated that GOx remained in its native biochemical functional form upon being embedded onto the rGO matrix. Cyclic voltammetry studies showed that the presence of mesoporous rGO greatly enhanced the direct electrochemistry and electrocatalytic properties of the GOx/rGO and Lac/rGO nanocomposites. The electron transfer rate constant between GOx and rGO was estimated to be 2.14 s −1 . The fabricated EBFC (GOx/rGO/FP-Lac/rGO/FP) using a single GOx/rGO/FP bioanode and a single Lac/rGO/FP biocathode provides a maximum power density (P max ) of 4.0 nW cm −2 with an open-circuit voltage (V OC ) of 0.04 V and remains stable for more than 15 days with a power output of ∼9.0 nW cm −2 at a pH of 7.4 under ambient conditions.