The Palladium/polydopamine (Pd/PDA) litchi-like nanoclusters are synthesized via a two-step route. The resultant product is characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and the electrochemical properties were evaluated by cyclic voltammetry (CV) and chronoamperometry. Notably, the as-prepared litchi-like Pd/PDA nanoclusters show superior catalytic properties for methanol electro-oxidation in an alkaline medium due to unique Pd dots adhered at PDA surface providing a large electrochemically active surface area (ECSA). Additionally, the high concentration of oxygen functional groups on PDA is essential to the removal of carbonaceous species from the adjacent at the Pd sites. This PDA-based straightforward synthesis strategy offers a new pathway for developing highly active electro-catalysts with aid of special organic polymer.