The design of efficient catalysts with atom clusters (ACs) and single atoms (SAs) as active sites for water splitting presents an effective approach for improving bifunctional electrocatalytic performance by synergistically promoting electron transport and proton transfer kinetics. In this work, a series of Fe2O3-supported noble metal catalysts (M = Ru, Rh, Pd, Ag) incorporating both ACs and SAs sites were developed, with detailed characterization identifying Ru ACs as the primary active centers. The designed-interfacial M-O-Fe bonds play a critical role in charge redistribution, subsequently enhancing electron and proton transfer kinetics. The resulting heterostructure optimizes both the electronic environment and active site accessibility, yielding exceptional electrocatalytic performance. Further density functional theory calculations demonstrate that the incorporation of Ru species leads to increased filling of antibonding orbitals and modulation of the d-band center, subsequently reducing the energy barrier of the rate-determining steps to −0.267 eV for HER and 1.522 eV for OER, respectively. Consequently, the representative Ru/Fe2O3 with Ru content of 1.1 wt.% achieves an OER overpotential of 189 mV and a HER overpotential of 21 mV at a current density of 10 mA cm−2. This study highlights a novel approach to the design of advanced bifunctional electrocatalysts by engineering interfacial bridge bonds.