This work describes first a 5-stack direct methanol fuel cell (DMFC) based on poly(3,4-ethylenedioxythiophene)modified paper (PEDOT/PB-DMFC), which acts as an energy source and biosensor, coupled to an electrochromic cell (EC). It is autonomous and monitors the biosensor response by color change, as appropriate for point-of-care (POC) applications. In detail, DMFC strips were developed from square Whatman paper, and the EC was made on baking paper treated with polydimethylsiloxane (PDMS). The PEDOT/PB-DMFCs operate in a passive mode with a few microliters of diluted methanol. The biosensor layer was obtained on the anode ink (a composite of EDOT, oxidized multiwalled carbon nanotubes, and carbon black with platinum and ruthenium) by electropolymerizing 3,4-ethylenedioxythiophene (EDOT), in situ, in the presence of L1CAM. Each PEDOT/PB-DMFC single cell generates a voltage in the range of 0.3−0.35 V depending on the cell, and a five-cell stack delivers a 1.5−1.6 V voltage range when fed with 0.5 M methanol. The fabricated PEDOT/PB-DMFC/biosensor was calibrated against L1CAM, showing linear responses from 1.0 × 10 −12 to 1.0 × 10 −8 M with a detection limit of 1.17 × 10 −13 M (single cell mode). When the EC was connected to the PEDOT/PB-DMFC device, a color gradient was observed. Overall, this work opens horizons to the use of biosensors even in places with energy scarcity and offers an alternative to reducing the current energy demand.