Eight heteroleptic nickel(II) complexes of the type [NiL1–4(co-ligand)] 1–8, where L1–4 = N 1,N 2-bis(5-substituted-2-hydroxybenzylidene)-1,2-ethylene/phenylene diimine and co-ligand = 2,2′-bipyridyl (bpy) or 1,10-phenanthroline (phen), have been synthesized and fully characterized by analytical and spectral methods. The six-coordinated octahedral geometry around the nickel(II) center was inferred from the electronic spectra of the complexes. Cyclic voltammetric studies of the complexes evidenced one-electron irreversible nature of reduction and oxidation process. The observed rate constant (k) values for the hydrolysis of 4-nitrophenylphosphate are in the range of 0.24–2.53 × 10−2 min−1. The obtained room temperature magnetic moment values (2.96–3.31 BM) lies within the range observed for octahedral nickel(II) complexes. Antioxidant studies suggest the considerable radical-scavenging potency of the complexes against DPPH radical. The DNA-binding studies of complexes with calf thymus DNA revealed intercalation with minor-groove mode of binding. The nuclease activity on supercoiled pBR322 DNA revealed the involvement of hydroxyl radical and singlet-oxygen as reactive oxygen species and complexes encourage binding to minor-groove.