A series of copper(II) and zinc complexes of 2-hydroxyacetophenone semicarbazones have been prepared and evaluated as superoxide dismutase (SOD) mimetics. The SOD-like activity of parent ligands and complexes were determined by the inhibition of nitroblue tetrazolium (NBT) reduction method, using xanthine/xanthine oxidase as the superoxide radical generator. The obtained results indicate that Cu(II) complexes exhibited the most potent SOD-like activities with the IC₅₀ values ranging from ca. 0.2 to 4 μM. Among copper complexes, 2-hydroxy-4-methoxyacetophenone semicarbazone analog was the most active compounds (IC₅₀ ≈0.2 μM).