Two novel complexes for Zn2+ and VO2+ ions, were prepared from tridentate dibasic chelating Schiff base ligand. 1-((3,5-di-tert-butyl-2-hydroxybenzylidene)amino)naphthalen-2-ol-5‑sodium sulfonate (DSHN), was the ligand used in this study. Alternative spectral tools were applied to elucidate structural composition of new compounds. Also, geometry optimization for all synthesizes was conducted by Gaussian09 program via DFT method, to obtain optimal structures and essential parameters. Moreover, the biochemical behavior for all synthesizes, was explored based on tested reactivity against various microbial strains and cancer cells (HCT-116, MCF-7, and HepG-2). The two complexes exhibited interestingly anti-proliferative potential against human cancer cell lines. The antioxidant behavior of the two complexes was studied by DPPH and SOD assays. Particularly, Zn(II) and VO(II) complexes presented more enhanced antimicrobial and anticancer features compared to the free ligand (DSHN), with superiority ...