The effects of hydroxypropyl-α-cyclodextrin (HP-α-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) on the twisted intramolecular charge transfer (TICT) emission of omeprazole (OMP) in aqueous solution were investigated by absorption and steady-state and time-resolved fluorescence techniques. The shorter wavelength (SW) band originates from the locally excited state and the longer wavelength (LW) band is due to the emission from a TICT state. The excited state fluorescence decay life time for the TICT emission was increased at higher CD concentration, whereas no significant change observed in the lower CD concentrations. The absorption and fluorescence spectral shifts and the size of the OMP suggest that OMP forms 1:1 inclusion complex at lower CD concentrations whereas 1:2 inclusion complex at higher CD concentrations. Semiempirical quantum optimization were also been carried out to assign the encapsulation of the OMP.