Enzymatic biofuel cell technology has demonstrated the possibility of producing electrical power from chemical energy using biological catalysts for powering portable and implanted electronic devices. However, this technology has been limited by insufficient power and shell life compared to existing commercial, non-biological fuel cells. During the last 20 years, significant advancements have been made in improving the overall performance of the biofuel cells with incorporation of hybrid nanostructures including carbon and metal based nanomaterials and combination thereof with enzymes. Typically, biofuel cell cathodes utilize a single enzyme system, while a cascade of reactions for deeper and more complete oxidation of fuel is frequently necessary at the anodes. Here, we present the feasibility of using glycerol for the development of alcohol based biofuel cell. For the first time, the biofuel cells were extended via the assembly of hybrid enzymatic anode and bilirubin oxidase (BOx) biocathode. The hybrid anode was integrated with non-enzymatic oxidation of glycerol by inorganic nanoparticles and enzymatic nanocomposite conversion of final byproduct to achieve a cascade of efficient energy conversion from glycerol. The constructed mediator-less and membrane-less biofuel cell demonstrated maximum open circuit potential (OCV) greater than 600mV, power output of 0.7mW/cm² and maximum current density of 3.0mA/cm² with 0.1M glycerol at neutral pH. The fuel cell demonstrated remarkable discharge capacity of 600mAh/g under 0.25mA constant current load. The enzymatic/non enzymatic hybrid strategy can be further extended to develop other alcohol based biofuel cells.