Classical extraction involves several time-consuming and costly steps using toxic solvents. Here, we combined the preparation of a cyclodextrin-based supramolecular deep eutectic solvent and the extraction of spent coffee grounds by microwave irradiation in a single step. We tested two new solvents, randomly methylated-β-cyclodextrin:propylene glycol and hydroxypropyl-β-cyclodextrin:ethylene glycol, and compared the results with two classical solvents, chloride:urea (1:2) and ethanol/water 80/20 vol%. We also used classical Soxhlet extraction. We calculated the sustainability of the process using ComplexGAPI. Results show that the optimal one-step extraction conditions were 15 min of irradiation at 80 °C with the addition of 10 wt% water. Under these conditions, the two new solvents showed higher extraction yields of antioxidants and polyphenols than choline chloride:urea (1:2) or ethanol/water 80/20 vol%. Similarly, the half maximal effective concentration and gallic acid equivalent of the Soxhlet extracts were 5 and 3 times lower, respectively, than those obtained with hydroxypropyl-β-cyclodextrin:ethylene glycol (1:40) 10 wt% water. The composition of the extracts from the one-step process was similar to that of the Soxhlet extract. Sustainability analysis revealed low energy consumption, reduced unitary operations and less waste production.