Direct methanol fuel cell (DMFC) with near-zero pollution emission, large energy density, and low operating temperature provides a beneficial and sustainable way for alleviating fossil energy crisis and ecological pollution issues. In this work, a systematic protocol was explored for the design of novel electrocatalyst based on PEDOT-PSS coated amino-functionalized SiO2 microspheres (SiO2–NH2@PEDOT-PSS) support, and then Pt nano-particles (NPs) were uniformly anchored for the anodic process of DMFCs. Characterization techniques, e.g. X-ray diffraction (XRD) and transmission electron microscopy (TEM) confirmed that the dispersity and homogeneity of Pt NPs on the surface of SiO2–NH2@PEDOT-PSS were markedly improved due to PEDOT-PSS modification, and the distribution of Pt NPs was in a smaller mean-size ~2.8 nm. Subsequently, X-ray photoelectron spectroscopy (XPS) study exposed fast electron shift phenomenon from SiO2–NH2@PEDOT-PSS support to Pt NPs in the catalyst. The various electrochemical tests such as cyclic voltammetry (CV), chronoamperometry (CA) and impedance spectroscopy (EIS) revealed that the prepared Pt/SiO2–NH2@PEDOT-PSS catalyst presented higher electrocatalytic efficacy, excellent durability with improved CO-tolerance towards methanol oxidation reaction rather than commercial Pt/C catalyst. These distinctive physical and chemical features of designed catalyst raise the spirit to design an efficient electrocatalyst based on Pt/SiO2–NH2@PEDOT-PSS in DMFC applications.