Zinc(II), copper(II), nickel(II) and cobalt(II) complexes of Schiff-bases, obtained by the condensation of 3 rd generation Cephalosporin e.g., Ceftriaxone, Cefixime, Cefotaxime, and Ceftazidime with the respective aldehydes such as furyl-2-carboxaldehyde, thiophene-2-carboxaldehyde, salicylaldehyde, pyrrol-2-carboxaldehyde and 3- hydroxynaphthalene-2-carboxaldehyde were synthesized and characterized by their physical, molar conductance, magnetic moments, and electronic spectral measurements (IR, 1 H and 13 C NMR and mass), analytical (CHN analysis) and thermal analyses data. Analytical data and electrical conductivity measurements indicated the formation of M:L (1:2) complexes of the type [M(L) 2 (H 2 O) 2 ] or [M(L) 2 (H 2 O) 2 ]Cl 2 [where M = Zn(II), Cu(II), Ni(II) and Co(II)] in which ligands act as bidentate towards divalent metal ions via azomethine-N and deprotonated-O of salicyl and naphthyal, furanyl-O, thienyl-S and XIIIdeprotonated pyrrolyl-N. The magnetic moments and electronic spectral data suggest octahedral geometry for these complexes. The main objective of present study is to highlight the potential of Cephalosporin derivatives as antimicrobial agents. The work comprises of the study of changes in antimicrobial activity of four cephalosporins, Ceftiaxone, Cefixime, Cefotaxime and ceftazidime by condensation of free amino group (NH 2 ) of these Cephalosporin with the carbonyl (HC=O) group of aldehydes to achieve the target of twenty new Cephalosporin derived Schiff bases (L 1 )-(L 20 ) and their metal complexation with Zn(II). Cu(II), Ni(II), Co(II) salts. The synthesized ligands, along with their metal complexes were screened for their antibacterial activity against different Gram-positive & Gram-negative (Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, Pseudomonas aeruginosa, Salmonella enteritidis and Klebsiella pneumonia) bacterial strains using agar-well diffusion method. The minimum inhibitory concentration (MIC) was observed and thereafter compared with the standard MIC’s of the respective drug by agar dilution method against both Gram positive and Gram-negative organisms so as to evaluate changes in antimicrobiological activity of the standard cephalosporins after azomethine formation with aldehydes and their metal interactions. The results of these studies show the metal complexes to be more antibacterial against one or more species as compared to the uncomplexed ligands. It was concluded that metal elements that are essential for our body mechanism either present in the body or coadminstered with vitamins markedly influence the MIC’s of antibiotics by producing synergism or antagonism.