Interactional behavior of bile salts, namely, sodium cholate (NaC) and sodium deoxycholate (NaDC), in the presence of an antibiotic drug, ceftriaxone sodium (Cft-Na), at different temperatures has been analyzed through volumetric, compressibility, viscometric, and proton nuclear magnetic resonance ( 1 H-NMR) studies. The volumetric and compressibility parameters have been calculated with the help of measured density (ρ) and speed of sound (u). Also, the knowledge on intermolecular interactions present in a ternary system consisting of bile salts in aqueous solution of drug has been procured from viscometric measurements. The variation in strength of the present intermolecular interactions in the system with temperature and concentration has been analyzed by carrying out the experiments at different temperatures, i.e., 293.15, 298.15, 303.15, 308.15, and 313.15 K, and drug concentrations, i.e., 0.005, 0.010, and 0.050 mol•kg −1 . The results have been interpreted by considering the cosphere overlap model, which confirm the presence of hydrophobic and hydrophilic interactions in the system. Also, the information obtained from density, speed of sound, and viscometric studies has been strengthened by analyzing the 1 H-NMR spectra. The study may be helpful in utilization of bile salts in pharmaceutical industries as a penetration enhancer.