<p>The hybrid nanocomposites advancements are crucial to the medicinal applications with biocompatible behavior. This work demonstrates the preparation of different chitosan-based nanocomposites of CS/rGO (NC-1), CS/rGO/HA (NC-2), CS/rGO/HA/CeO₂ (NC-3), and CS/rGO/HA/CeO₂/PMMA (NC-4) for the biological applications. A cost-effective and straightforward chemical methodology was used for their synthesis. The structural and optical characteristics of the synthesized nanocomposites were thoroughly examined using Fourier transform infrared spectroscopy, X-ray diffraction, and UV–Vis analyses. Morphological imaging revealed modified surface properties and a quasi-spherical structure with agglomerated grains in the prepared nanocomposites. The biological and therapeutic effects of these composites were assessed through antibacterial, cytocompatibility, and wound healing studies. Notably, the NC-3 and NC-4 nanocomposites exhibited enhanced antibacterial activity against both gram-negative (<i>P. aeruginosa</i> and <i>E. coli</i>) and gram-positive (<i>S. aureus</i> and <i>B. subtilis</i>) microorganisms. Cell viability assessments on MG-63 osteoblast cells indicated improved cell adhesion with the NC-4 composites. Furthermore, the in vitro wound scratch assay demonstrated that the NC-4 nanocomposite significantly promoted cell proliferation and migration, effectively facilitating wound healing within 48&#xa0;h. Thus, the NC-4 nanocomposite emerges as a promising candidate for antibacterial and bone regenerative applications.</p>