In this study, sulfated-titania (SO<inf>4</inf>2--TiO<inf>2</inf>) was employed as a sustainable, green catalyst to synthesize a series of novel phenoxy Schiff bases (3a-3g) through a microwave-assisted, solvent-free green protocol involving 2-phenoxyaniline and various aromatic aldehydes, achieving yields of 90–99 % within 4 min. The catalyst has been studied by FT-IR, powder X-ray diffraction, and SEM with EDS. The structures of the synthesized Schiff's bases (SBs) were elucidated through physicochemical and spectroscopic analyses like FT-IR, 1H & 13C NMR, and SC-X ray diffraction. Specifically, compounds 3d and 3g exhibited crystalline structures in the monoclinic and orthorhombic systems, respectively, with space groups denoted as C-1c and P-2<inf>1</inf>. In-depth understanding of the synthesized SBs in their gaseous state, computational investigations encompassing molecular orbitals, chemical reactivity, stability, and molecular electrostatic potential are essential. Furthermore, antimicrobial assessment highlighted the effectiveness of the SBs toward a variety of gram-negative and gram-positive strains of bacteria, as well as fungal strains. Molecular docking studies employing AutoDock revealed notable binding interactions, with the most favourable binding energy of -7.22 kcal/mol observed in association with the Human Carbonyl Reductase (4Z3D) protein. In addition, in silico ADMET prediction showed enhanced pharmacokinetic profiles and reduced acute oral toxicity. © 2025 Elsevier B.V., All rights reserved.