Deep eutectic solvents (DESs) have been intensively pursued in the field of separation processes, catalytic reactions, polymers, nanomaterial science, and sensing technologies due to their unique features such as the low cost of components, ease of preparation, tunable physicochemical properties, negligible vapor pressure, non-toxicity, renewability, and biodegradability in the recent decade. Considering these appealing merits, DESs are widely used as extraction agents, solvents and/or catalysts in the desulfurization process since 2013. This review is focused on summarizing the physicochemical properties of DESs (i.e., freezing point, density, viscosity, ionic conductivity, acidity, hydrophilicity/hydrophobicity, polarity, surface tension, and diffusion) to some extent, and their significant advances in applications related to desulfurization processes such as extraction desulfurization, extraction–oxidation desulfurization, and biomimetic desulfurization. In particular, we systematically compile very recent works concerning the selective aerobic oxidation desulfurization (AODS) under extremely mild conditions (60 °C and ambient pressure) via a biomimetic approach coupling DESs with polyoxometallates (POMs). In this system, DESs act as multifunctional roles such as extraction agents, solvents, and catalysts, while POMs serve as electron transfer mediators. This strategy is inspirational since biomimetic or bioinspired catalysis is the “Holy Grail” of oxidation catalysis, which overcomes the difficulty of O₂ activation via introducing electron transfer mediators into this system. It not only can be used for AODS, but also paves a novel way for oxidation catalysis, such as the selective oxyfunctionalization of hydrocarbon. Eventually, the conclusion, current challenges, and future opportunities are discussed. The aim is to provide necessary guidance for precisely designing tailor-made DESs, and to inspire chemists to use DESs as a powerful platform in the field of catalysis science.