A novel series of transition metal complexes of Cu(II) and Zn(II), including: [Cu(L1)2]: C1, [Cu(L2)2]: C2, [Cu(L3)2]: C3, [Cu(L4)2]: C4, [Zn(L1)2]: Z1, [Zn (L2)2]: Z2, [Zn (L3)2]: Z3, and [Zn (L4)2]: Z4, with four halogenated bis-N,O-bidentate Schiff base ligands (HL1: 2-ethoxy-6-[(4-fluorophenyl)iminomethyl]phenol; HL2: 2-ethoxy-6-[(4-chlorophenylimino)methyl]phenol; HL3: 2-ethoxy-6-[(4-bromophenyl)iminomethyl]phenol; HL4: 2-ethoxy-6-[(4-iodophenylimino)methyl]phenol have been synthesized and characterized by elemental analyses, FT-IR, UV–Vis and 1H NMR spectroscopic techniques. Furthermore, the crystal structures of HL2, HL4, Z1 and Z2 were determined by single crystal X-ray analysis. These bidentate ligands coordinated to the metal(II) ions through the deprotonated phenolic oxygens and the azomethine nitrogens. The X-ray diffraction analysis revealed that Z1 and Z2 adapted distorted tetrahedral geometries. Theoretical calculation of the synthesized compounds, carried out by DFT as well as TD-DFT using B3LYP method with employing the Def2-TZVP basis set, indicated that the calculated results are in accordance with the experimental findings. NBO analysis has been used to elucidate charge transfer information of the HL2, HL4, Z1 and Z2. Moreover, binding ability of the Schiff base ligands and their metal complexes with FS-DNA was studied by spectroscopic and computational methods. The results of both methods showed that the ligands bound in minor grooves of DNA. The oxygen of the ethoxy group has played an important role in DNA binding investigations.