The study aims to scrutinize the mixed micellization and interfacial behavior of two 1-alkyl-3-butylimidazolium based surface-active ionic liquids (SAILs) i.e., 1-decyl-3-butylimidazolium bromide [C10bim][Br] and 1-tetradecyl-3-butylimidazolium bromide [C14bim][Br] under the influence of streptomycin sulphate (SS) drug in 5 mM concentration in aqueous media. Imidazolium-based SAILs have unique physicochemical properties and greater surface activity than conventional surfactants, which allows them to increase drug permeability, making them better drug carriers than currently available formulations. To fully utilize [C14bim][Br] and [C10bim][Br] in drug delivery applications, deep insight into the interactions occurring in the mixed micellar [C10bim][Br]/[C14bim][Br] systems in the drug’s presence are necessary to be examined. Thus, the study is conducted using conductivity and surface tension measurement techniques to fully exploit the self-assembly, micellization behavior and interactions occurring in the pure and mixed micellar system of [C10bim][Br]/[C14bim][Br] in water and 5 mM of SS solution in aqueous media. For this, various thermodynamic, surface-active and mixed micellar parameters of micellization have been calculated and analyzed with respect to change in mole fraction, temperature and addition of SS in solution.