A series of Cu(II) complexes of 5,5-dimethyl-2-(2-arylhydrazono)cyclohexane-1,3-dione (HL_n) were synthesized by the coupling of dimedone with aniline and its derivatives. These ligands and their Cu(II) complexes were characterized by elemental analyses, IR, ¹H NMR, ¹³C NMR, UV–Visible, X-ray diffraction analysis and magnetic measurements. Spectral studies revealed that the ligand exist in an internally hydrogen bonded keto-hydrazone form rather than the azo-enol form. The ligands (HL_n) acts as a monobasic bidentate ligand by coordinating via the nitrogen atom of the hydrazone moiety (NH) with deprotonation and oxygen atom of the carbonyl (CO) group. The optimized bond lengths, bond angles and quantum chemical parameters of the complexes were calculated. The calf thymus DNA binding activity of the ligands and their Cu(II) complexes were studied by absorption spectra and viscosity measurements. The antimicrobial activities of ligands and Cu(II) complexes were tested against Gram negative bacteria (Escherichia coli), Gram positive bacteria (Staphylococcus aureus) and fungal (Candida albicans). The cytotoxic activity of ligands and Cu(II) complexes was tested against two human cancer HePG-2 (Hepatocellular carcinoma) and MCF-7 (breast cancer). The antioxidant activities of ligands and Cu(II) complexes were performed by ABTS method.