Large proteins remain inaccessible to structural NMR studies because of their unfavorable relaxation properties. Their solubilization in the aqueous core of reverse micelles, in a low-viscosity medium, represents a promising approach, provided that their native tertiary structure is maintained. However, the use of classical ionic surfactants may lead to protein unfolding, due to strong electrostatic interactions between the polar head groups and the protein charges. To design reverse micelles in which these interactions are weakened, a new zwitterionic surfactant molecule was synthesized and studied by high-resolution NMR spectroscopy, for which cytochrome C and 15N-labeled ubiquitin were used as guest candidates. At different ionization states, both proteins are encapsulated in the absence of salts or other additives, in a folded conformation similar to the native one.