Ten new Schiff base diols derived from isovanillin and syringaldehyde were virtually designed using in-silico tools. Analysis of absorption, distribution, metabolism, and excretion (ADME) properties using SWISS ADME tool evidenced the drug likeness of the Schiff base diols.The designed compounds showed no violation to Lipinski‟s „rule of five‟ except for molecular weights of few compounds. The physicochemical properties showed that all designed Schiff base diols have good oral absorption and adequate skin permeability. Geometry optimizations of the diols were done using Density Functional Theory (DFT) calculations using the Gaussian 09W software package. Further DFT calculations were used to investigate HOMO, LUMO, Mulliken charges, and theoretical modes of vibrations of the Schiff base diols. HOMO and LUMO studies showed that among the ten Schiff base diols, compound 5 is the most stable( ΔE= 0.178) and compound 9 is the most reactive with lowest energy gap( ΔE= 0.035). Molecular docking was used to predict the binding ability of the Schiff base diols with cortisone reductase deficiency 2 (CORTRD2). The compounds 3,5, and 7 exhibited strong interactions with (PDB CODE: P28845) receptor via hydrophobic interaction and hydrogen bonding.