Developing highly active and durable catalyst is of pivotal importance in fuel cells, owing to excessive consumption of fossil fuels. Herein, porous dendritic PtRuPd nanospheres (PtRuPd NSs) were synthesized by a facile hexadecylpyridinium chloride (HDPC)-mediated one-pot aqueous method with ascorbic acid (AA) as the reducing agent. The as-obtained PtRuPd NSs displayed high-efficient catalytic activity and durability for ethylene glycol oxidation reaction (EGOR) and oxygen reduction reaction (ORR). It exhibited enlarged mass activity (MA, 1.368 A mg−1) compared to commercial Pt/C (1.100 A mg−1) for EGOR. Besides, the onset potential (Eonset, 0.930 V) and half-wave potential (E1/2, 0.852 V) of PtRuPd NSs were more positive relative to homemade PtPd NSs (0.905 and 0.840 V), PdRu NSs (0.895 and 0.839 V), and commercial Pt/C (0.910 and 0.822 V) toward ORR. This work provides some valuable guidelines for producing novel trimetallic nanocatalysts in fuel cells.