<p>Four novel ON donor Schiff bases (E)-3-((4-phenoxyphenylimino)methyl)benzene-1,2-diol (HL<sub>1</sub>),(E)-3-((4-(4-biphenyloxy)phenyliminomethyl)benzene-1,2-diol (HL<sub>2</sub>), (E)-3-((4-naphthoxyphenylimino)methyl)benzene-1,2-diol (HL<sub>3</sub>), (E)-3-((4-(2-naphthoxy)phenylimino)methyl)benzene-1,2-diol (HL<sub>4</sub>) and their copper(II) complexes bis((E)-3-((4-phenoxyphenylimino)methyl)benzene-1,2-diol) copper(II) (Cu(L<sub>1</sub>)<sub>2</sub>) bis((E)-3-((4-(4-biphenyloxy)phenylimino)methyl)benzene-1,2-diol) copper(II) (Cu(L<sub>2</sub>)<sub>2</sub>), bis((E)-3-((4-naphthoxyphenylimino)methyl)benzene-1,2-diol) copper(II) (Cu(L<sub>3</sub>)<sub>2</sub>), bis((E)-3-((4-(2-naphthoxy)phenylimino)methyl)benzene-1,2-diol) copper(II) (Cu(L<sub>4</sub>)<sub>2</sub>) have been synthesized and characterized by spectroscopic (FTIR, NMR, UV–visible) and elemental analysis. The crystal structures of HL<sub>1</sub>, HL<sub>2</sub>, HL<sub>3</sub><sub>,</sub> and HL<sub>4</sub> have been determined, which reveal intramolecular N-H⋯O (HL<sub>1</sub>, HL<sub>2</sub>, HL<sub>3</sub><sub>,</sub> and HL<sub>4</sub>) hydrogen bonds in the solid state. Keto-amine and enol-imine tautomerism is exhibited by the Schiff bases in solid and solution states. The Schiff bases and their copper(II) complexes have been screened for their biological activities. In antimicrobial assays (antibacterial and antifungal), HL<sub>4</sub> showed promising results against all strains through dual inhibition property while the rest of the compounds showed activity against selective strains. On the other hand, in cytotoxic, DPPH, and inhibition of hydroxyl (OH) free radical-induced DNA damage assays, the results were found significantly correlated with each other, <i>i.e.</i> the ligands HL<sub>1</sub> and HL<sub>2</sub> showed moderate activity while their complexes Cu(L<sub>1</sub>)<sub>2</sub> and Cu(L<sub>2</sub>)<sub>2</sub> exhibited prominent increase in activity. As the results of these assays are supporting each other, it represents the strong positive correlation and antioxidant nature of investigated compounds.</p
