High cost and restricted activity of electrocatalysis are the major challenges for hydrogen generation and biosensors. In this work, we provided a one-pot synthesis of Cu_xPd_y alloy nanoparticles (NPs) with controllable atomic ratio and “clean surface”. Benefiting from the preferable d-band structure, the Cu₆₂Pd₃₈ NPs exhibited a lower overpotentials in the hydrogen evolution reaction (HER) over the full pH range. In the acidic media, Cu₆₂Pd₃₈ NPs achieved a low overpotential of 28.12 mV for HER, which was 25.73% of Pd NPs. In the neutral solution, the overpotential by Cu₆₂Pd₃₈ NPs is only 41.71% for that by uncleaned CuPd NPs. In alkaline media, the overpotential by Cu₆₂Pd₃₈ NPs was declined from 38.01 to 20.20 mV after 720 min yielding hydrogen, which was only 53.14% for the initial overpotential. As applied in biosensor, the synergistic effect of Cu and Pd accelerated the kinetics of electrocatalytic process, resulting in an enhanced performance. The glucose sensor constructed by Cu₆₇Pd₃₃ exhibited a wider detection range up to 100.0 mM. And the sensitivity is 379.4 µA/(mM·cm²), which is ca. 4.63 and 14.09 folds for that by pure Cu NPs and Pd NPs, respectively. An optimal atomic percent would be conducive to optimize electrocatalytic activity of Cu_xPd_y alloy. The volcano plots for Cu_xPd_y would open up a new avenue for designing electrocatalysis with rationalized cost and optimized performance.