Schiff-base copper(II) complexes were prepared using macrocyclic ligands, synthesized by condensation of diethylmalonate with Schiff bases derived from o-phenylenediamine and Knoevenagel condensed -ketoanilides (obtained by the condensation of acetoacetanilide and substituted benzaldehydes). The ligands and their copper complexes were characterized by microanalytical, mass, UV-Vis, IR, 1 H-NMR, ESR and CV studies, as well as conductivity data. Microanalytical, mass and magnetic moment analyses are consistent with formation of monomeric [CuL]Cl 2 . Spectral studies indicate square-planar geometry around copper. The smaller grain sizes found from XRD data suggest that these complexes are polycrystalline with nanosized grains. The SEM images of [CuL 1 ]Cl 2 have leaf-like morphology. The in vitro biological screening of the investigated compounds against the bacteria Escherichia coli, Klebsiella pneumoniae, Salmonella typhi, Pseudomonas aeruginosa and Staphylococcus aureus and fungi Aspergillus niger, Rhizopus stolonifer, Aspergillus flavus, Rhizoctonia bataicola and Candida albicans were tested by the well diffusion method to assess growth inhibition. A comparative study of MIC values of the Schiff-base ligands and their complexes indicate that the complexes exhibit higher antimicrobial activity than the free ligands.