The present study reports the synthesis, structural characterization of Ni(II) (1,3) and Cu(II) (2,4) metal complexes of Schiff-base (L) derived from 5H-[1,2,4]triazino[5,6-b]indol-3-amine and salicylaldehyde moiety. The coordination sphere of Cu(II)/Ni(II) was completed by tethering secondary ligand 2,2′–Bipyridine and 1,10 phenanthroline to obtain the final complexes 1–4, respectively. The spectral analysis of complexes 1 and 3 suggested square planar geometry while complexes 2 and 4 acquire the octahedral geometry around the metal centers. In vitro DNA binding profiles of the newly synthesized metal complexes 1–4 with calf thymus DNA (CT DNA) were explored by employing electronic absorption titrations and fluorescence spectral studies. The results revealed that complexes 1–4 bind to DNA through electrostatic surface binding mode along with partial intercalation in the minor groove. Moreover, complexes 3 and 4 have stronger DNA binding propensity with higher intrinsic binding constant K_b values of 1.9 × 10⁴ and 4.8 × 10⁴ M^–1, respectively. Additionally, HSA binding studies of ligand L and metal complexes 1–4 support the static quenching mechanism and alterations in the microenvironment around Trp–214 residues causing conformational distortions in the HSA secondary structure. Furthermore, molecular docking studies of complexes 3 and 4 with DNA and HSA confirms that both specifically binds in G–C rich regions of the DNA minor groove and subdomain IIA pocket of HSA near the Trp–214 residue.