Constructing low-cost, high-efficiency, and earthabundant electrocatalysts for enhancing the energy efficiency of water splitting is highly desirable. Herein, we employed a facile strategy of V cation doping and Ru nanoparticles modification to construct a multifunctional NiFe-LDH electrocatalyst (Ru/V-NiFe-LDH) on a nickel foam (NF) substrate. This Ru/V-NiFe-LDH/NF catalyst exhibited exceptional catalytic activity (e.g., small overpotentials and a Tafel slope) and good stability in HER, OER, and UOR, indicating significantly lower than that of commercial Pt−C and RuO 2 . These excellent electrochemical properties primarily resulted from the effects of V doping and Ru nanoparticles modification, which altered the surface charge state of the NiFe-LDH matrix, led to electron rearrangement, accelerated charge transfer, provided more active sites, and enhanced intrinsic catalytic activity. Moreover, when assembled into a two-electrode system with Ru/V-NiFe-LDH/NF for overall water/urea splitting, a low cell voltage of 1.53 and 1.40 V @10 mA cm −2 was afforded. Furthermore, this system also exhibited outstanding stability, with only a 19% decay in high current density at 50 mA cm −2 after 48 h. These performances far surpass those of RuO 2 ||Pt−C and most nonprecious-metal catalysts. This work highlights the rational design of high-performance multifunctional electrocatalysts for overall water/urea splitting applications.