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Introduction and aim: At present, several microbial diseases are prominent and of concern worldwide. The intent of this study was to examine the antibacterial potential of newly synthesized tetradentate macrocyclic complexes against different bacterial strains. The macrocyclic scaffold has gained attention as a biologically active class of supramolecular chemistry due to its unique properties and ability to target various microorganisms. Thus, the goal of the present study was to develop a series of biologically active transition metal-based macrocycles. Material and methods: All macrocyclic compounds were synthesized by a template method and validated by molar conductivity, elemental studies, and spectral and magnetic studies. Antibacterial activities of all metal complexes were evaluated against Escherichia coli (MTCC 739) and Staphylococcus aureus (MTCC 731) bacterial strains by taking ampicillin as a standard reference drug. DNA photocleavage potential was explored using agarose gel electrophoresis. Results: Results revealed the formation of novel macrocyclic complexes via tetra nitrogen bond trapping of metals. Copper complexes have strong potential against S. aureus bacteria as copper and nickel both show good DNA photocleavage potential. Concusion: The findings endorse the biomedical relevance of these macrocyclic scaffolds, suggesting avenues for further exploration in targeted drug delivery and potential clinical applications. The proposed octahedral geometry for the complexes enhances our understanding of their structural aspects. This research contributes substantively to the field, laying the foundation for future investigations in advanced antimicrobial design and application. [ABSTRACT FROM AUTHOR]