We report the use of cubic palladium nanoparticles (PdNPs) for the catalytic oxidation of hydrazine for use in a hybrid self-powered N2H4 sensor. Multiwalled carbon nanotube electrodes were prepared and functionalized with PdNPs by drop casting, confining the colloidal suspension of nanoparticles into the 3D-carbon nanotube matrix support. Electron microscopy and electrochemical characterization experiments were performed and confirmed the presence, uniform distribution, and accessibility of the metallic particles. Cubic PdNPs with an average diameter of 22.5 nm were investigated for their catalytic hydrazine oxidation capacities at varying hydrazine concentrations. Application of the PdNPs for electrochemical detection of hydrazine was demonstrated using a hybrid fuel cell setup with the PdNPs-based electrode as the anode and a bilirubin oxidase bioelectrode as the oxygen-reducing cathode. The self-powered hybrid sensor exhibits linear hydrazine detection from 0.02 to 4.00 mmol L−1 and a sensitivity of 53 ± 3 mW cm−2 mmol−1 L. When using the air-breathing cathode setup, the fuel cell could deliver a maximal current and power output of 1.23 ± 0.08 mA cm−2 and 267 ± 10 μW cm−2 respectively. PdNPs supported on carbon nanotube electrodes are thus promising catalytic materials for self-powered sensing and hybrid fuel cell applications via consumption of environmental contaminants.