The nature of functionalization of alkyl chains of imidazolium-based surface active ionic liquids (SAILs) with amide or ester moiety led to contrasting complexation behavior toward the globular protein, bovine serum albumin. This prompted us to further investigate the SAIL-dependent colloidal behavior of another globular protein, beta-lactoglobulin (beta LG), to probe the origin of varying structural transformations in globular proteins induced by SAILs. Herein, we investigated the colloidal systems of beta LG, rich in beta-sheet structure, in the presence of four structurally different SAILs using a multitechnique approach. The complexation behavior, both at the air-solution interface and in bulk, is supplemented by different techniques. Docking studies have complemented the obtained experimental results. The specificity of structure, H-bonding ability of SAILs, and inherent structure of protein are found to govern their complexation behavior in terms of size, shape, and polarity of protein-SAIL complexes along with varying degrees of structural alterations in globular proteins. The present work is expected to be very useful in establishing a deep understanding of the structure-property relationship between the nature of proteins and SAILs for their complexation and colloidal behavior for various biomedical applications.