Deep eutectic solvents (DES) can be prepared with ease by mixing a suitable combination of a hydrogen-bond acceptor (HBA) and a hydrogen-bond donor (HBD) using a molar ratio. The prepared DES can have various unexplored applications, which depend on their unique physicochemical properties. Among these applications, DES have been recently studied for drug delivery and drug solubilization. The possibility of having hydrogen-bonding and polar/nonpolar interactions with a drug molecule can help DES solubilize the sparingly soluble drug molecules. The nature of these interactions can be modulated by a change in temperature, concentration, or even by the presence of moisture. Interactions between DES and drug molecules mediated by water were studied by measuring the volumetric properties and UV− visible spectra of caffeine (CAF) in aqueous DES solutions as a function of concentration and temperature. PEG-400 and citric acid were mixed in an appropriate molar ratio for the preparation of PEGylated DES. The volumetric properties were studied by measuring the density and speed of sound at (293.15−318.15) K and 0.1 MPa. UV−visible studies were performed at 298.15, 308.15, and 318.15 K. Apparent molar volumes, infinite dilution partial molar volumes, and volumetric transfer parameters were evaluated and interpreted to explain the solute−solute, solute−solvent, and solute−cosolute interactions between CAF and DES in aqueous mixtures. The results suggest the presence of various interactions among the components of DES and CAF. Further, dimerization of CAF caused a decrease of absorbance with an increase in cosolute concentration.