In this work, we report paper-based microbial fuel cells (MFCs) that produce high power and current densities from one drop of bacteria-containing liquid. The devices feature (i) a simple and versatile fabrication technique by using paper as a substrate and (ii) an exceptional performance by incorporating novel nanostructured polymers, PAA-Poly (amic) acid) and PPDD-Poly(pyromellitic dianhydride-p-phenylene diamine), into the paper substrate. Four 3-D MFC configurations were designed by using different numbers of 2-D sheets of paper layers. Each device integrated four functional compartments (i.e. anode, reservoir, proton exchange membrane, and air-cathode) into one, two, three or four paper layers, respectively. The nanostructured polymers were engineered as a proton exchange membrane to enhance ion traveling efficiency or an oxygen mitigating layer to prevent diverting electrons away from the anode. Among the four MFC devices with different numbers of layers, two-layer paper-based MFC generated the highest current density of 47UA/cm2 and power density of 4UW/cm2, both of which are substantially greater than achieved by previous paper-based MFCs and even comparable to that of conventional micro-sale counterparts.