Nucleic acids and proteins have primarily evolved to conduct sophisticated functions in aqueous environments. Here, we challenge this paradigm by incorporating these biomolecules into anhydrous DESs. The “designer” character of DESs opens the possibility to control the solvation properties through changes in the solvents’ constituents. This ultimately allows to modulate the conformation and self-association of these biomolecules. Our efforts focus on understanding the underlying interactions that define biomolecular behavior in DESs, aiming at predicting the required solvent properties to induce a pre-designed functional response.