The present investigation reports the importance of the S and R forms of fluoxetine, as an antidepressant with regards to the chirality taking different types-of interactions associated with the neurotransmitter, serotonin. The goal of the present study is to provide predictions and to help experimental and theoretical studies toward understanding the chirality of fluoxetine in drug-ligand interaction, associated with serotonin-reuptake inhibitor drug design studies. Several different conformations for serotonin and fluoxetine complexes have been considered for quantum mechanical calculations. Both the S and R forms of fluoxetine associated with serotonin and fluoxetine complexes are found to be similar in total energy and binding energy values. The present study also supports the conformational effect of the 3-phenyl group of fluoxetine as stereo independent and is consistent with in vitro and in vivo data which indicates that the the eudismic ratio of fluoxetine enantiomers is near unity. The calculated highest stabilization energy values, binding energy values, both in the gas and aqueous phases at MP2/6-31+G*//B3LYP/6-31+G* identify the most possible stable conformer for the serotonin-fluoxetine complex.