The equilibrium stabilities and the folding rates of membrane-bound proteins are determined by hydrophobic and polar intermolecular contacts with their environment as well as by intramolecular packing and conformational dynamics. The contributions of these factors, however, remain elusive and might vary considerably among proteins. Mistic from Bacillus subtilis is a particularly intriguing example of an α-helical protein that associates with membranes in spite of its unusual hydrophilicity. In micelles, Mistic is stabilized by hydrophobic and polar interactions with detergents, but it is unclear whether and how these intermolecular contacts are coupled to structural and dynamic adaptations of the protein itself. Here, we investigated the packing and the conformational dynamics of Mistic as functions of detergent headgroup chemistry and chain length, employing single-molecule Förster resonance energy transfer spectroscopy and time-resolved intrinsic tryptophan fluorescence spectroscopy. Surprisingly, in nonionic detergents, more effective hydrophobic burial and, thus, greater protein stability with increasing hydrophobic micellar thickness were accompanied by a gradual loosening of the helical bundle. By contrast, Mistic was found to assume a stable, compact fold in zwitterionic detergents that allowed faster dynamics on the nanosecond timescale. Thus, intramolecular packing per se is insufficient for conferring high protein stability; instead, enhanced nanosecond dynamics and, consequently, greater conformational entropy in the compact folded state account for Mistic’s high equilibrium stability and fast folding rates in zwitterionic micelles even at the expense of less effective hydrophobic burial.