Mirtazapine (MTZ) is a racemic antidepressant drug, consisting of its S(+) and R(-) - enantiomers in a 50:50 mixture. MTZ has been investigated for its potential in the treatment of Rett syndrome, a neurodevelopmental disorder affecting 1/10.000 young females worldwide. However, the mechanisms of action of MTZ are still unclear. To gain new insights into the pharmacological effects of MTZ, the in-silico prediction of novel targets for MTZ represents a valuable approach. S-MTZ and R-MTZ chemical structures were downloaded from PubChem database to perform a screening of S-/R- MTZ versus 25.717 human pockets using the BioGPS software. The resulting molecule-pocket affinity scores were compared to a background distribution composed by scores obtained from 10 inactive drugs, previously identified via an in vitro drug screening carried out in our laboratory, and were referred to as Zz-score. Zz-score comprises a z-score for the molecule and a z-score for the pocket. Finally, the pockets with high affinity for S- and R-MTZ were docked within the corresponding protein complexes on BioGPS software. Filtering the results with Zz-score ≥2.0, z-pocket ≥1.0 and z-molecule ≥1.0, the in-silico prediction retrieved 16 target proteins for S-MTZ and 14 for R-MTZ, 5 of which were in common between S- and R-MTZ. The pathway enrichment analysis found 24 enriched pathways for S-MTZ and 25 for R-MTZ of which 11 were in common between the two enantiomers. These findings highlight the potential of in-silico methods to predict MTZ-target proteins interactions, contributing to develop more effective and relevant treatments for Rett syndrome.