The water-soluble phosphonate functionalized spherical platinum nanoclusters (Pt-NCs) composed of primary nanoparticles are synthesized by the thermal decomposition of platinum(IV)-complex. The size, morphology and structure of Pt-NCs are analyzed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Attachment of phosphonate groups on Pt surface is confirmed by Fourier transform infrared (FT-IR) spectroscopy, X-ray photoelectron spectroscopy (XPS), and zeta potential analysis. The phosphonate functionalized Pt-NCs efficiently suppress the oxygen reduction reaction (ORR) while fully preserving the Pt-like activity for the hydrogen peroxid reduction reaction. Importantly, at certain cathodic potential, only reduction reaction of hydrogen peroxide occurs at the Pt-NCs surface. Consequently, the phosphonate functionalized Pt-NCs can be used to fabricate a new kind of hydrogen peroxide electrochemical sensor with high performance in the presence of oxygen. Under optimized experimental conditions, the hydrogen peroxide electrochemical sensor shows fast response (less than 2s) and wide linear range (1.0×10−6–1.0×10−3 M) in the presence of oxygen. The results presented here indicate an important new direction in the quest to design selective catalysts for the fabrication of noble-metal based H2O2 electrochemical sensor.