Ionic liquids (ILs) are versatile solvents for a broad range of biotechnological applications. Recent experimental and simulation results highlight the potential benefits of dilute ILs in aqueous solution (aqueous ILs) in order to modify protein and DNA structures systematically. In contrast to a limited number of standard co-solutes like urea, ectoine, trimethylamine-N-oxide (TMAO), or guanidinium chloride, the large amount of possible cation and anion combinations in aqueous ILs can be used to develop tailor-made stabilizers or destabilizers for specific purposes. In this review article, we highlight common principles and differences between aqueous ILs and standard co-solutes with a specific focus on their underlying macromolecular stabilization or destabilization behavior. In combination with statistical thermodynamics theories, we present an efficient framework, which is used to classify structure modification effects consistently. The crucial importance of enthalpic and entropic contributions to the free energy change upon IL-assisted macromolecular unfolding in combination with a complex destabilization mechanism is described in detail. A special focus is also set on aqueous IL-DNA interactions, for which experimental and simulation outcomes are summarized and discussed in the context of previous findings.