Recent studies have focused on tailoring the catalytic currents of multicopper oxidase (MCO) enzymes-based biocathodes to enhance oxygen reduction. Biocathodes modified with natural substrates specific for MCO enzymes demonstrated drastic improvement for oxygen reduction. Performance of 1-pyrenebutanoic acid, succinimidyl ester (PBSE), and 2,5-dimethyl-1-phenyl-1H-pyrrole-3-carbaldehyde (Di-Carb) oriented bilirubin oxidase (BOx) modified gas diffusion biocathode has been highly improved by incorporating hematin, a porphyrin precursor as electron transfer enhancement moiety. Hematin modified electrodes demonstrated direct electron transfer reaction of BOx exhibiting larger O 2 reduction in current density in phosphate buffer solution (pH 7.0) without the need of a mediator. A remarkable improvement in the catalytic currents with 2.5-fold increase compared to non-hematin modified oriented BOx electrodes was achieved. Moreover, a mediatorless and compartmentless glucose/O 2 biofuel cell based on DET-type bioelectrocatalysis via the BOx cathode and the glucose dehydrogenase (GDH) anode demonstrated peak power densities of 1 mW/cm 2 at pH 7.0 with 100 mM glucose/10 mM NAD fuel. The maximum current density of 1.6 mA/cm 2 and the maximum power density of 0.4 mW/cm 2 were achieved at 300 mV with nonmodified BOx cathode, while 3.5 mA/cm 2 and 1.1 mW/cm 2 of current and power density were achieved with hematin modified cathode. The performance improved 2.4 times which attributes to the hematin acting as a natural precursor and activator for BOx activity enhancement.