In the current study, a set of 1,2,3-triazolyl-based metronidazole hybrids (7a-m) was synthesized from the reaction of 2-methyl-5-nitro-1-(prop‑2-yn-1-yl)-1H-imidazole with β-azido alcohols in the presence of [CuL] as catalyst. The chemical structures of the synthesized compounds were characterized using different spectroscopic techniques (IR, ¹H NMR, ¹³C NMR, Mass) and elemental analysis. Then, the in vitro cytotoxic activity of the synthesized compounds 7a-m were investigated against human melanoma cell line A375, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cytotoxic results showed that these compounds have moderate anticancer activity compared to methotrexate as a reference drug. Among all the synthesized compounds, compound 7l was found to be the most potent derivative with IC₅₀ value of 62.5 µM. Finally, the molecular docking studies and molecular dynamic simulation were carried out to obtain the binding mode of these derivatives in the binding site of receptor. The results of docking studies were in good agreement with the in vitro cytotoxic results.