This study focuses on the synthesis and characterization of novel Schiff base ligands derived from 2,5,6-trisub-stituted imidazothiadiazole and their corresponding Ag(I) complexes. The ligands and complexes were structurally elucidated using techniques including FTIR, 1H and 13C NMR, ESI-MS, and thermogravimetric analysis. Molecular docking studies revealed that the ligands exhibit promising binding affinities to target proteins, with ligand 16 showing the highest interaction potential. The in vitro cytotoxicity of the synthesized compounds was assessed against the A549 non-small cell lung cancer (NSCLC) cell line using the MTT assay. Among the tested compounds, Ag(I) complexes demonstrated significantly enhanced anticancer activity compared to their parent ligands, with complex 17 exhibiting the highest potency. Furthermore, docking simulations supported these findings. These results highlight the potential of these Ag(I) complexes as candidates for further development in cancer therapeutics.