Vacancy engineering has been one of the most vital strategies to enhance the catalytic activity of oxygen evolution reactions (OER) and biomass oxidation reactions (BOR). Herein, 3D antler-like VC-Co3O4/CoSe2 arrays grown on Ni foam with abundant O and Se dual vacancies were constructed via a hydrothermal approach followed by etching engineering. The rich oxygen vacancies optimize the adsorption of intermediates, increase the number of active sites, and reduce charge transfer impedance. Meanwhile, Se vacancies can effectively regulate the electronic structures to enhance the intrinsic activities of active sites, which further promote the electrocatalytic performance. Thanks to the synergistic effect of dual vacancies, the designed VC-Co3O4/CoSe2/NF catalyst presents enhanced catalytic activity for OER, with reduced overpotential of 263 mV to achieve a current density of 30 mA cm−2. Moreover, VC-Co3O4/CoSe2/NF also demonstrates remarkable urea oxidation reaction (UOR) and glycerol oxidation reaction (GOR) performance, which just requires a low potential of 1.43 and 1.36 V at 30 mA cm−2, respectively, and maintains long-term durability over 65 h. More importantly, the VC-Co3O4/CoSe2/NF is assembled into a cell, the GOR//HER system supplies a lower cell voltage of 1.47 V to afford 10 mA cm−2 in comparison with OER//HER. This work opens up a promising avenue for the development of high-efficiency and low-cost multifunction electrocatalysts to promote the sustainable development for hydrogen production.