1-(2-((4-Bromophenyl)amino)-2-oxoethyl)pyridin-1-ium chloride Schiff base (CH-Py) was prepared via reacting (CH) with pyridine-3-carboxaldehyde, followed by reacting the product with N-(4-bromophenyl)-2-chlor- oacetamide. The structure of the resulting CH derivative was determined via 1 HNMR and FTIR. The CH-Py derivative was converted into nanoparticles (CH-Py-Cl NPs) using sodium tripolyphosphate (TPP). Additionally, the nanocomposites (CH-Py-Cl NPs) were prepared discretely by dispersion of 3.0 % Se and 3.0 % Fe2O3 nano particles into the CH-Py-Cl NPs matrix to derive the products denoted as CH-Py-Cl/Se and CH-Py-Cl/Fe, respectively aiming to develop innovative effective chitosan Schiff base nanocomposites towards H. pylori. Anti-H. pylori activity of CH-Py-Cl NPs, CH-Py-Cl/Fe, and CH-Py-Cl/Se were found to be at a minimal inhibitory concentrations MIC value of 62.5, 31.25, and 15.62 mu g/mL, indicating that CH-Py-Cl/Se possessed the highest biological activity in our investigation. Finally, the CH-Py-Se-NPs nanocomposite was examined for its in vitro cytotoxicity against colon cancer cell lines (Caco-2). The results obtained indicated that the developed CH-Py-Cl/ Se showed toxic effects on Caco-2 cells, with an IC50 value of 124.52 +/- 1.15 mu g/mL.