Geometrical structure, electronic and optical properties, electronic absorption spectra, thermodynamic properties, natural charge distribution, MEP analysis, and charge transfer analysis of trans and cis structures of chlorprothixene drug have been investigated with DFT and TDDFT methods. The results of the computations show that the calculated quantum quantities of the cis isomer of chlorprothixene are in agreement with the activity of cis-chlorprothixene as a drug. Cis structure of chlorprothixene has slightly better absorption properties than the trans structure on the basis of TDDFT calculations. The NLO quantities of the cis structure are higher than the trans structure, and the chemical hardness of the cis isomer, is smaller than the trans isomer which specifies that the reactivity and charge transfer of the cis structure of chlorprothixene is higher than the trans structure. The MEP maps of both conformations of chlorprothixene show that the top of the N atom and the around of the S and Cl atoms of the molecule are proper regions for electrophilic reactions. The calculated thermodynamic parameters illustrate that these parameters are improving with increasing temperature because of the enhancement of molecular vibrational intensities with temperature. (C) 2017 Elsevier B.V. All rights reserved.