<p>This study aimed to synthesize and evaluate zinc oxide (ZnO) nanoparticles functionalized with chitosan (ZnO CS) and chitosan-terephthalic acid (ZnO CS-TPA) for enhanced stability and biological activity in cancer therapy applications. The nanoparticles were characterized using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), Field Emission Scanning Electron Microscopy (FESEM), Dynamic Light Scattering (DLS), and Zeta Potential measurements. XRD analysis revealed crystallite sizes of 244.75 Å for ZnO CS and 169.95 Å for ZnO CS-TPA, with microstrain values of 1.28 × 10⁻⁵ and 4.20 × 10⁻⁵, respectively. FESEM images showed distinct morphologies, with ZnO CS forming rod-like structures (lengths of 500–2000 nm) and ZnO CS-TPA exhibiting spherical particles ( &lt;100 nm). DLS analysis indicated bimodal size distributions, with Z-average hydrodynamic diameters of 990.2 nm (ZnO CS) and 611.1 nm (ZnO CS-TPA), and polydispersity indices of 0.768 and 0.474, respectively. Zeta potential values were −52.8 mV for ZnO CS and −47.3 mV for ZnO CS-TPA, indicating good colloidal stability. Cytotoxicity studies against colon cancer cells (HT-29) using the MTT assay demonstrated significant dose-dependent activity, with ZnO CS-TPA showing enhanced efficacy compared to ZnO CS (viability reduction of ~70% vs. ~50% at 64 µg/mL). These findings suggest that surface modification of ZnO nanoparticles with chitosan and terephthalic acid enhances their stability and efficacy as potential agents for targeted cancer therapy.</p> Graphical Abstract <p></p>