Five new copper(II) niflumate complexes, [Cu(en)2(nif)2], 1, [Cu(unsym-dmen)(nif)2], 2, [Cu(pn)2(nif)2][Cu(pn)2(H2O)2](nif)2 3, [Cu(β-pic)2(nif)2], 4, [Cu(γ-pic)2(nif)2] 5 (where en = ethylenediamine, pn = propan-1,3-diamine, unsym-dmen = 1,1-dimethyl-ethylenediamine, β-pic = 3-methylpyridine, γ-pic = 4-methylpyridine, nif = niflumate) have been synthesized by using appropriate starting materials and methanol-water (4:1 v/v) as solvent. All the above synthesized complexes 1–5 have been characterized by spectroscopic methods (UV–Vis, FT-IR, and EPR). The structures of complexes 1, 3 and 5 have been unambiguously determined by single crystal X-ray structure determination which clearly revealed that these complexes are mononuclear complexes. The structure of complex 4 has been optimized by DFT calculations. In all complexes 1–5, niflumate ligand shows direct coordination to central copper(II) ion leading to covalent character of these complexes, although the complex 3 also contains cationic moiety [Cu(pn)2(nif)2]2+ and two nifumate ions. The ability of all the complexes to show cytotoxicity against human cancer cell lines has also been evaluated.