As a unique two-dimensional (2D) material, 2D noble metal-based intermetallic compounds (IMCs) have attracted much attention in electrocatalysis owing to their exceptional physical and chemical properties. However, the synthesis of 2D noble metal-based IMCs with well-defined structures remains challenging. This comprehensive review begins by delving into the morphology modulation of 2D noble metal-based IMCs, highlighting their key synthesis strategies, such as the CO-assisted and halide ion modulation methods. Subsequently, we discuss the advantages of 2D noble metal-based IMCs in electrocatalysis, including oxygen reduction reaction, alcohol oxidation reaction, formic acid oxidation reaction, and hydrogen evolution reaction. Finally, the main challenges and perspectives for the future development of 2D noble metal-based IMC electrocatalysts are presented to accelerate their promising commercialization.