<p>In the present work, new nanocomposites based on the Zn metal-organic framework (ZIF-8) were developed. The efficacy of the as-synthesized nanocomposites as a delivery system for the norfloxacin drug (NOR) was investigated. Four nanocomposites were obtained by combining ZIF-8 with sodium montmorillonite (ZIF-8/Na⁺-Mt), magnetite nanoparticles with sodium montmorillonite (Fe₃O₄/Na⁺-Mt), ZIF-8 and magnetite nanoparticles (Fe₃O₄ NPs) with sodium montmorillonite (ZIF-8/Fe₃O₄/Na⁺-Mt) and ZIF-8, coated magnetite nanoparticles with Cetyltrimethylammonium bromide with sodium montmorillonite (ZIF-8/CTAB@Fe₃O₄/Na⁺-Mt). The synthesized nanocomposites were characterized by several tools. NOR drug was loaded on these nanocomposites through a batch adsorption process. The highest loading of NOR was observed for ZIF-8/CTAB@Fe₃O₄/Na⁺-Mt nanocomposite with a percentage of 99.9%. The pH-dependent in vitro release of NOR from the as-synthesized carriers was accomplished. By combining ZIF-8 with Na⁺-Mt and coating Fe₃O₄ NPs with CTAB, a successful release of NOR (with a ratio of 52.98%) from ZIF-8/CTAB@Fe₃O₄/Na⁺-Mt nanocomposite in a strong acidic medium was achieved without dissolution of ZIF-8 and Fe₃O₄ NPs. NOR is released from ZIF-8/CTAB@Fe₃O₄/Na⁺-Mt with the highest accumulation ratio of 99.56% within 502&#xa0;h (21 days) at pH 8.5. The mechanism of release was studied using zero-order, first-order, Higuchi and Korsmeyer-Peppas models. The as-prepared nanocomposites exhibited antibacterial activity against <i>Staphylococcus aureus</i> (<i>S. aureus</i>) and <i>Escherichia coli</i> (<i>E. coli</i>) except Fe₃O₄/Na⁺-Mt nanocomposite. As a result, ZIF-8/CTAB@Fe₃O₄/Na⁺-Mt nanocomposite could be a promising carrier for NOR antibiotic in different pH mediums.</p>