Drug-surfactant catanionic mixtures having advantages in many applicable aspects encourage us to examine the interactions of an anti-inflammatory drug, diclofenac sodium (DFNa), with surface active ionic liquids (Es), 1-dodecyl-3-methylimidazolium bromide (C(12)mimBr) and 1-tetradecyl-3-methylimidazolium bromide (C(14)mimBr), in aqueous medium. The surface activity of IL solution get remarkably customized upon binding with DFNa reflected as changed composition and reduced thickness of mixed monolayer. Modification to emission and absorption profile of DFNa upon addition of ILs come out to be a result of their strong synergistic interactions. These strong interactions lead to the formation of four distinct interactional states; ion-pairs, pre-micelles, DFNa-rich micelles, IL-rich micelles. Electrostatic interaction played a major role in stabilizing ion pairs where as hydrophobic, cation-pi as well as pi-pi interactions come into play to stabilize further formed species. A detailed understanding of the energetic of DFNa-IL interactions in these different interactional states has been studied by isothermal titration calorimetry. Additionally effect of added IL on the voltammetric response of DFNa, zeta potential and hydrodynamic diameter (D-h) values provides further support for the existence of various species.