Palladium modified cerium oxide (CeO2 or ceria) nanoparticles (Pd-CeO2) were prepared by depositing palladium nanoparticles with average diameters of 3–5nm on the surface of CeO2 via chemical reduction of the precursor (Pd2+). The electrocatalytic activity of Pd-CeO2 toward the detection of different important compounds (i.e. glucose, ascorbic acid (AA), dopamine (DA) and uric acid (UA)) has been investigated. Compared with the CeO2 or Pd modified electrode, the Pd-CeO2 modified electrode has higher catalytic activity toward the oxidation of glucose, AA, DA, and UA. A nonenzymatic glucose sensor was developed for the sensitive and selective detection of glucose. Moreover, in the mixture of AA, DA and UA, obvious electrochemical potential separations among the three detected peaks were observed, making the simultaneously determination of AA, DA and UA possible. The attractive features of Pd-CeO2 provide potential applications in sensor and biosensor design.