In this paper, RGO/PANI/Pt@FeOx with a three-dimensional multilayer structure is successfully prepared by the one-pot method, in which the introduction of PANI prevents GO from agglomerating, and also plays a crucial supporting role in the three-dimensional multilayer structure. SEM and TEM images confirm that the catalyst has a three-dimensional multilayer structure, and Pt nanoparticles are uniformly dispersed on the surface of PANI/RGO, with an average particle size of 3.2 nm. The electrochemical evaluation clearly shows that the mass activity of 3D multilayer RGO/PANI/Pt@FeOx (1.573 Amg−1Pt) is three times than that of Pt/C. After 3600 s, it retained mass activity is seven times than that of Pt/C. In addition, 3D multilayer RGO/PANI/Pt@FeOx catalyst has better CO tolerance than Pt-RGO/PANI, Pt/C and Pt-RGO. These results mainly originate from that the three-dimensional multilayer structure provides a larger specific surface area, N species in PANI can be conducive to the uniform dispersion of platinum, and the existence of FeOx improves the catalytic efficiency of Pt and the rate of water splitting due to bi-functional mechanism, consequently enhancing the CO tolerance of catalyst. Thereby, 3D multilayer RGO/PANI/Pt@FeOx can be utilized as a promising methanol oxidation catalyst.