Angiogenesis is the formation of new blood vessels and capillaries from pre-existing blood vessels. In general, it plays an important role in the development of tumors, as tumors never grow beyond 2 to 3 mm without angiogenesis processes which supply the essential nutrient to the tumor. Therefore, blocking the angiogenesis process is one of the promising strategies to inhibit cancer cell growth. Metals are essential for several biochemical reactions in living organisms. It is a cellular component selected by nature to function in many biological processes. Metal complexes show a broad range of pharmacological activity and considerable efforts are made for the development of metal complexes as drugs. Encouraged by this information, the metal complexes of Cobalt(II), Nickel(II), Zinc(II), Cadmium(II), and Copper(II) derivative of N, N’ Bis-(3,4,5-trimethoxy benzylidene)–benzene–1,2-diamine have been synthesized from o-phenylene diamine in the alcoholic medium. The metal complexes (M1−M5) were characterized using different techniques like 1H NMR, Fourier-transform infrared spectral data, mass spectral data, thermo gravimetric studies, magnetic susceptibility data, molar conductance, ESR, and micro-elemental analysis. The result obtained from the characterization results reveals that all the metal complexes (M1−M5) obtained were square planar except one which was octahedral configuration. The DNA binding, cleavage and anti-angiogenesis activity shown by the complexes (M1−M5) were significantly better than the ligand. Also, complexes M2 and M3 showed the highest anti-angiogenic activity and decreasing intensity of lane as compared with other synthetic complexes. In-silico docking simulations predicted the anti-angiogenesis activity of the complexes against homo sapiens of VEGFR-2 and exhibited prominent interactions at the active site pocket region. Moreover, density functional theory (DFT) was applied to calculate HOMO-LUMO, energy gap, and other parameters under PBE1PBE functional with lanl2dz basis sets.