A green synthetic pathway for two mononuclear M(II)-complexes (M = Ni2+ as a non-oxy-metal ion and ZrO2+ as an oxy-metal ion, NiLig and ZrOLig, respectively) of an imino-naphthalenol sodium sulfonate ligand (H2Lig) was followed. Using various physico-chemical tools, their chemical compositions were elucidated. The material-studio package was applied to confirm the structures of NiLig and ZrOLig via the DFT method. The biological potential of the ligand (H2Lig) and its NiLig and ZrOLig complexes was investigated for different microbial strains as well as different cancer cell lines. The redox potential of the newly synthesized complexes was evaluated using different biochemical assays, e.g. DPPH and SOD assays. The NiLig and ZrOLig complexes exhibited improved antimicrobial and anticancer activities as compared to the free ligand (H2Lig). Accordingly, the ZrOLig complex was the most active biological reagent. The binding nature of the M2+ complexes to calf thymus DNA (ctDNA) was examined by UV–Vis. spectrophotometry and viscosity measurements. Both the Ni2+ and ZrO2+ complexes interestingly demonstrated anti-proliferative action against the human cancer cell lines. Such ctDNA interactions were examined theoretically by molecular docking. The approaches between the exported in-silico drug-likeness and the considered DNA interaction study were explored. The binding action between the M2+ complex and DNA would be within the electrostatic minor groove, intercalation and replacement binding modes.