The agglomeration of metal catalysts can limit the performance of fuel cells. Herein, an easy, scalable, one-pot microwave-assisted method is proposed to introduce guanine, which is a nucleobase found in deoxyribonucleic acid and ribonucleic acid, to the reduced grapheme oxide-supported palladium via noncovalent functionalization. Considering the abundant amino, amide, and imino functional groups of guanine that act as anchoring sites, palladium nanoparticles of various shapes such as triangular, rectangular, circular, and diamond are uniformly distributed. The guanine itself is revealed to be catalytically active toward methanol oxidation reaction, serving as second catalyst. Consequently, the as-produced nanocomposite has a larger electrochemically active surface area (111.98 m(2) g(-1) vs. 63.80 m(2) g(-1)), greater methanol electro-oxidation ability (1017.42 mA mg(-1) vs. 359.80 mA mg(-1)), and higher stability in alkaline medium than its counterpart without guanine.