The global increase in antimicrobial resistance has emphasized the urgent need for novel and effective antiseptic agents. This challenge has spurred interest in developing new chemical entities, including coordination compounds that can enhance antimicrobial efficacy and offer alternative strategies for infection control. In view of this growing antimicrobial challenge, isoniazid Schiff bases, namely N-(2-hydroxy-5-bromobenzylidene)isonictinoylhydrazide(L1) and N-(2-hydroxy methoxybenzylidene) isonictinoylhydrazide (L2), and their Cu(II) and Co(II) complexes are reported. The compounds were characterized based on melting point, FTIR, 1H and 13C NMR and elemental analysis. The Schiff bases act as tridentate ligands bonding through azomethine nitrogen, phenolic, and carbonyl oxygen atoms. The in vitro antibacterial study was performed on the compounds against Staphylococcus aureus ATCC 25923, Enterococcus feacalis ATCC 29212, Escherichia coli 2592 and Pseudomonas aeruginosa 27853. The Schiff base ligands and their complexes were observed to exhibit a strong inhibitory effect on S. aureus bacteria, with the cobalt complexes exhibiting the greatest effect. This implies that these compounds may be considered promising candidates for further exploration as potential antiseptic agents subject to future toxicological evaluation and formulation studies.