High-entropy spinel compounds (HESs), as a typical class of high-entropy materials (HEMs), represent a novel frontier in the search for next-generation catalysts. Their unique blend of high entropy, compositional diversity, and structural complexity offers unprecedented opportunities to tailor catalyst properties for enhanced performance (i.e., activity, selectivity, and stability) in heterogeneous reactions. However, there is a gap in a critical review of the catalytic applications of HESs, especially focusing on an in-depth discussion of the structure-property-performance relationships. Therefore, this review aims to provide a comprehensive overview of the development of HESs in catalysis, including definition, structure features, synthesis, characterization, and catalytic regimes. The relationships between the unique structure, favorable properties, and improved performance of HESs-driven catalysis are highlighted. Finally, an outlook provides guidance for unveiling the complexities of HESs and advancing the field toward the rational design of efficient energy and environmental materials.