This review summarizes recent advances in improving the efficiency of ethanol electrooxidation (EOR) in direct ethanol fuel cells (DEFCs), focusing on strategies to enhance the cleavage of the C–C bond in ethanol. DEFCs are promising for their high volumetric energy density, efficiency, and environmental benefits. However, the chemically stable C–C bond in ethanol limits the efficiency of EOR, with state-of-the-art Pt and Pd catalysts achieving only 7.5% C–C bond cleavage efficiency. Recent research has introduced various strategies to improve this efficiency, including constructing core–shell nanostructures with alloying effects, doping other metal atoms into Pt and Pd catalysts, engineering composite catalysts with interface synergism, and introducing cascade catalytic sites. Key strategies include alloying Pt and Pd with oxophilic metals to enhance catalytic performance through bifunctional mechanisms, such as increasing lattice strain and modulating electronic structures. Additionally, the introduction of cascade catalytic sites, like the Pt/Al₂O₃@TiAl composite catalyst, enables ethanol dehydration and ethylene oxidation, achieving 100% C1 pathway selectivity. Interface synergism, such as in Pd-Au heterophase nanosheets, also enhances catalytic efficiency by reducing energy barriers for C–C bond cleavage. Doping effects, such as introducing Rh or Ga atoms, improve catalytic activity and stability by modifying surface sites and reducing CO poisoning. The review highlights the importance of optimizing catalyst structures to achieve high C1 pathway selectivity and stability, while minimizing toxic intermediates. Future research should focus on developing more efficient and stable catalysts for complete ethanol oxidation, with a focus on reducing energy barriers and enhancing catalytic performance. The integration of multiple strategies, including alloying, doping, and interface synergism, is crucial for advancing DEFC technology and achieving practical applications.This review summarizes recent advances in improving the efficiency of ethanol electrooxidation (EOR) in direct ethanol fuel cells (DEFCs), focusing on strategies to enhance the cleavage of the C–C bond in ethanol. DEFCs are promising for their high volumetric energy density, efficiency, and environmental benefits. However, the chemically stable C–C bond in ethanol limits the efficiency of EOR, with state-of-the-art Pt and Pd catalysts achieving only 7.5% C–C bond cleavage efficiency. Recent research has introduced various strategies to improve this efficiency, including constructing core–shell nanostructures with alloying effects, doping other metal atoms into Pt and Pd catalysts, engineering composite catalysts with interface synergism, and introducing cascade catalytic sites. Key strategies include alloying Pt and Pd with oxophilic metals to enhance catalytic performance through bifunctional mechanisms, such as increasing lattice strain and modulating electronic structures. Additionally, the introduction of cascade catalytic sites, like the Pt/Al₂O₃@TiAl composite catalyst, enables ethanol dehydration and ethylene oxidation, achieving 100% C1 pathway selectivity. Interface synergism, such as in Pd-Au heterophase nanosheets, also enhances catalytic efficiency by reducing energy barriers for C–C bond cleavage. Doping effects, such as introducing Rh or Ga atoms, improve catalytic activity and stability by modifying surface sites and reducing CO poisoning. The review highlights the importance of optimizing catalyst structures to achieve high C1 pathway selectivity and stability, while minimizing toxic intermediates. Future research should focus on developing more efficient and stable catalysts for complete ethanol oxidation, with a focus on reducing energy barriers and enhancing catalytic performance. The integration of multiple strategies, including alloying, doping, and interface synergism, is crucial for advancing DEFC technology and achieving practical applications.