Quercetin and caffeic acid are bioactive phytochemicals with significant pharmaceutical value due to their antioxidant, anti-inflammatory, and therapeutic properties. The growing demand for efficient and environmentally friendly extraction methods has spurred interest in green solvents such as deep eutectic solvents (DESs). In this study, a choline chloride–malic acid (ChCl–MA) DES was evaluated as a sustainable alternative to conventional solvents like ethanol for extracting quercetin and caffeic acid. Density Functional Theory (DFT) calculations were used to examine the molecular interactions and extraction potential of ChCl–MA compared to ethanol. All computations were performed using the wB97X-D functional, which accounts for dispersion interactions, with initial geometries optimized at the PM3 level. A dual basis set (6-31G(d)/3-21G*) was applied in the vacuum (gas phase) to ensure reliable results. The ChCl–MA DES was found to be thermodynamically stable and chemically more reactive than ethanol, as indicated by its lower HOMO–LUMO energy gap. It also exhibited stronger binding interactions with the target compounds: –1.63 eV for quercetin and –0.35 eV for caffeic acid, compared to ethanol’s –0.30 eV and –0.33 eV, respectively. These findings suggest that ChCl–MA may offer enhanced extraction potential relative to ethanol. However, it is important to note that these conclusions are based on vacuum (gas-phase) DFT simulations, which do not fully account for solvent-phase dynamics (solvation effect) or entropy effects. Therefore, while the results offer valuable theoretical insight into solvent–solute interactions, further experimental and solution-phase computational studies are necessary to validate the practical efficiency of ChCl–MA in real extraction scenarios.