Herein we present the results obtained in the in silico ADME screening and drug-likeness evaluation of three Schiff bases based on vanillin aldehyde. As an amine counterpart, the selenourea, urea and thiourea were used. According to the obtained results, all three compounds have demonstrated optimal lipophilicity and moderate solubility necessary for the achievement of good bioavailability when administrated orally. Ii was also observed that all compounds have potential to be well absorbed into systematic circulation in GIT (gastrointestinal tract), without possibility to cross blood-brain barrier. The urea-based compound has showed no potential to inhibit any of five P450 isoform. The target screening has indicated that the family of cytosolic proteins and enzymes were the most probable physiological targets for the screened compounds.