A simple approach to the synthesis metal complexes and copper, zinc nano particles size (CuNPs, ZnNPs) of novel Schiff base of sulfonamide ligand (HL) resulted from the condensation of sulfametrole [N '-(4-methoxy-1,2,5-thiadiazol-3-yl]sulfanilamide and 1-(2-Furanyl) ethanon. The metal complexes and copper, zinc nano particles size (CuNPs, ZnNPs) of HL ligand were synthesized and characterized using different physico-chemical studies as elemental analyses, mass spectra, conductivity measurement, UV-vis Spectra, solid reflectance, IR spectra,, 1 H NMR spectra, magnetic susceptibility, thermal analyses (TGA and DTA), (TEM) Transmission Electron Microscope and their microbial and anticancer activities. The spectroscopic data of the complexes suggest their 1:2(L:M) complex structures. Also the spectroscopic studies suggested the octahedral structure for all complexes. The size and morphology investigation of copper and zinc nano particles (CuNPs, ZnNPs) with (HL) ligand by TEM images indicate that the copper and zinc nano (CuNPs, ZnNPs) show spherical shape with core shell of HL ligand. The synthesized Schiff base and its metal complexes, CuNPs, ZnNPs were screened for their bacterial, antifungal and anticancer activity. The activity data show that the metal complexes, CuNPs and ZnNPs to be more potent than the parent HL Schiff base ligand. Also the data show that the CuNPs and ZnNPs more potent than the metal complexes and than HL free ligand .