Spent coffee grounds (SCGs) are a waste product with no relevant commercial value. However, SCGs are rich in extractable compounds with biological activity. To add value to this coffee byproduct, water and aqueous solutions of cholinium-based ionic liquids (ILs) were studied to extract caffeine from SCGs. In general, all IL aqueous solutions lead to higher extraction efficiencies of caffeine than pure water, with aqueous solutions of cholinium bicarbonate being the most efficient. A factorial planning was applied to optimize operational conditions. Aqueous solutions of cholinium bicarbonate, at a temperature of 80 °C for 30 min of extraction, a biomass–solvent weight ratio of 0.05 and at an IL concentration of 1.5 M, made it possible to extract 3.29 wt% of caffeine (against 1.50 wt% obtained at the best conditions obtained with pure water). Furthermore, to improve the sustainability of the process, the same IL aqueous solution was consecutively applied to extract caffeine from six samples of fresh biomass, where an increase in the extraction yield from 3.29 to 13.10 wt% was achieved. Finally, the cholinium bicarbonate was converted to cholinium chloride by titration with hydrochloric acid envisioning the direct application of the IL-caffeine extract in food, cosmetic and nutraceutical products. The results obtained prove that aqueous solutions of cholinium-based ILs are improved solvents for the extraction of caffeine from SCGs, paving the way for their use in the valorization of other waste rich in high-value compounds.