Selective oxidative depolymerization of a lignocellulosic biomass is the first step in the valorisation process. Chemical oxidations generally require hazardous reagents and harsh reaction conditions; thus, the resulting produced compounds are low-value molecules or complicated mixtures. Laccases are copper ion-containing oxidases and catalyze the oxidation of polyphenol or amine derivatives using molecular oxygen; laccase-mediated reaction systems thus allow the depolymerization of lignocellulosic compounds and the decomposition of aromatic pollutants in wastewater. However, due to the short distance between the active site and the surface of the laccase, the reactivity of laccase is influenced by the reaction conditions, in particular, the solvent system. Ionic liquids (ILs) and deep eutectic solvents (DESs) have now been acknowledged as not only new reaction media but also as activating agents of biocatalysts. In order to improve the activity or increasing the tolerance of laccases against ILs or DESs, three methods have been developed: the first is the direct evolution of the enzyme that is a very powerful tool for tailoring the enzyme, the second is the design of supporting materials including ILs for the immobilization of a laccase, and the third is modification of the surface of a laccase protein by chemical methods or protein engineering. This review examines laccase-mediated reactions in ILs and DESs focusing on how laccase contributes to sustainable chemistry; using laccase-mediated reactions, the depolymerization of lignocellulosic compounds, phenolic compounds, and synthetic dyes has now been accomplished. Since the reactions were accomplished under hazardous chemical reagent-free conditions, it is expected that investigation in this field of laccase-mediated oxidation might become even more important in sustainable chemistry.