In this study, we have reported the binding interaction and photophysics of a nonsteroidal anti-inflammatory drug (NSAID) indomethacin (IMC) in the presence of different micelles. We have used several spectroscopic techniques such as UV-vis absorption, steady state fluorescence and time-resolved fluorescence emission spectroscopy. The spectral properties of IMC were modulated in the presence of micelles compared to that in neat water. The weak emitting drug molecule (IMC) becomes highly fluorescent after binding with the micelles. The fluorescence quantum yield and fluorescence lifetime increase in the presence of micelles compared to those in neat water. The isothermal titration calorimetry (ITC) method was used to study the binding interaction of IMC with different micelles. The thermodynamic parameters and the nature of binding between IMC and different micelles have been estimated. Moreover, addition of KCl salt in the respective micelles releases IMC molecule from the micelles to the aqueous medium. This study will help elicidate the binding behavior of IMC in the presence of different micelles for possible use as potential drug delivery systems.