This study determined the optimal conditions for the deep eutectic solvent (DES) pretreatment of sugarcane leaves and the best fermentation mode for hydrogen and methane production from DES-pretreated sugarcane leaves. Choline chloride (ChCl):monoethanolamine (MEA) is the most effective solvent for removing lignin from sugarcane leaves. The optimum conditions were a ChCl: MEA molar ratio of 1:6, 120 °C, 3 h, and substrate-to-DES solution ratio of 1:12. Under these conditions, 86.37 ± 0.36% lignin removal and 73.98 ± 0.42% hemicellulose removal were achieved, whereas 84.13 ± 0.77% cellulose was recovered. At a substrate loading of 4 g volatile solids (VS), the simultaneous saccharification and fermentation (SSF) and separate hydrolysis and fermentation (SHF) processes yielded maximum hydrogen productions of 3187 ± 202 and 2135 ± 315 mL H2/L, respectively. In the second stage, methane was produced using the hydrogenic effluent. SSF produced 5923 ± 251 mL CH4/L, whereas SHF produced 3583 ± 128 mL CH4/L. In a one-stage methane production process, a maximum methane production of 4067 ± 320 mL CH4/L with a substrate loading of 4 g VS was achieved from the SSF process. SSF proved to be more efficient than SHF for producing hydrogen from DES-pretreated sugarcane leaves in a two-stage hydrogen and methane production process as well as a one-stage methane production process.