The purpose of this study was to investigate the effect of chitosan (CS) and Alginate (Alg) polymers concentrations and CaCl2 concentration on metronidazole (MET) drug loading (LE), size particles and zeta potential. Nanocomposites were prepared by ionotropic pregelation method. A (21 *31 *21) *3= 36 full factorial design (FFD) was used to predict statistical equation and responses. The MET-CS-AlgNPs nanocomposites were characterized by X-ray diffraction, Fourier-transform infrared spectroscopy, thermal gravimetric analysis, scanning electron microscope and in vitro drug release studies. All data indicated the presence of drug into MET-CS-AlgNPs nanocomposites. The release profile of MET-CS-AlgNPs nanocomposites was found to be sustained