Metal complexes of Co(II), Ni(II) and Cu(II) complexes (1–3) with a new Schiff base (HL) have been prepared and characterized by elemental analyses IR, UV–Visible, magnetic measurements, 1H NMR, 13C NMR, and X-ray diffraction analysis. Coats-Redfern and Horowitz-Metzger techniques are used to measure the thermodynamic parameters of the ligand and its complexes. The spectral data indicated that the ligand (HL) acts as a monobasic tridentate coordinating via the oxygen of the carbonyl group in the enol form, the nitrogen atom of the azomethine (–C=N–) group and phenolic –OH group. On the basis of magnetic and electronic spectral data, an octahedral geometry for Co (II), Ni (II) and Cu (II) complexes have been proposed. The molecular modeling using DFT method is drawn showing the bond lengths, bond angles and quantum chemical parameters. Absorption spectra and viscosity measurements have examined the calf thymus DNA binding behavior of the ligand and its complexes. The docking active site interactions were evaluated to predict the activity of HL against COVID-19 by binding with SARS-CoV-2 principal protease that recovered from the RCSB protein data bank with PDB ID: 6Y84 and its anticancer activity with prostate cancer receptor 3qum. Therefore, HL is worth further investigations and clinical trials as a possible therapeutic agent for prostate cancer and COVID-19 disease caused by the novel SARS-CoV-2. Evaluation results of synthesized complexes against the human cancer cell lines MCF-7 and HepG-2 were published in comparison with positive controls in the viability assay of vinblastine and colchicine. DPPH free radical-scavenging assays used to determine the in vitro antioxidant activity of all complexes. Moreover, the ligand and some complexes were screened for in vitro antibacterial activity against Staphylococcus aureus as Gram +ve bacteria and Escherichia coli (E. coli) as Gram -ve bacteria using inhibition zone diameter.