The development of non-enzymatic and highly active electrocatalysts for glucose oxidation with excellent durability for blood glucose sensors has aroused widespread concern. In this work, we report a fast, simple, and low-cost NaBH4 reduction method for preparing ultrafine ternary PtPdCu alloy nanowires (NWs) with a 3D network nanostructure. The PtPdCu NWs catalyst presents significant efficiency for glucose oxidation-reduction (GOR), reaching an oxidative peak-specific activity of 0.69 mA/cm2, 2.6 times that of the Pt/C catalyst (0.27 mA/cm2). Further reaction mechanism investigations show that the NWs have better conductivity and smaller electron transfer resistance. Density functional theory (DFT) calculations reveal that the alloying effect of PtPdCu could effectively enhance the adsorption energy of glucose and reduce the activation energy of GOR. The obtained NWs also show excellent stability over 3600 s through a chronoamperometry test. These self-supported ultrafine PtPdCu NWs with 3D networks provide a new functional material for building blood glucose sensors and direct glucose fuel cells.