The surface tension study of the surface-active drugs streptomycin sulphate and diphenhydramine hydrochloride has been carried out with three uni-univalent and three bi-univalent electrolytes viz. NaCl, KCl and RbCl (0.01 mol.kg-1), and MgCl2, CaCl2 and SrCl2, (0.002 mol.kg-1) at temperature range of 298.15 to 313.15 K. The interfacial parameters like maximum surface excess concentration ( Γmax), minimum area per surfactant molecule (Amin), and surface pressure at CMC (Πcmc) have been explored. The results represent the stronger affinity between drug-electrolyte molecules, which lower the surface tension values. The CMC relations govern the hydrophobic and hydrophilic interactions in ternary system (water-drug-electrolyte). Further, the addition of electrolytes lowers the total number of drug molecules at the interface, correlated with increase in Amin, and decrease in Γmax and Πcmc. Thermodynamics of micellization directs about the work done for micellization, and lighten the surface and bulk properties of drugs.