This study investigated the synthesis and characterization of carboxymethyl cellulose (CMC) derived from wheat husk cellulose and evaluated its antimicrobial efficacy. Cellulose was extracted using acidified sodium chlorite and subsequently converted to CMC through etherification involving sodium hydroxide and monochloroacetic acid. The process resulted in a cellulose yield of 15.6% and a CMC yield of 60.8%, with a degree of substitution (DS) of 0.2. Fourier-transform infrared (FT-IR) spectroscopy confirmed successful chemical modification, indicated by the appearance of a carbonyl absorption band at 1640 cm⁻¹. X-ray diffraction (XRD) analysis showed a decrease in crystallinity in the CMC compared with the native cellulose, while scanning electron microscopy (SEM) revealed a shift from a slightly cracked to a smoother surface morphology in the CMC. The antimicrobial properties of the synthesized CMC and zinc oxide-incorporated CMC (ZnO-CMC) biofilms were tested against Escherichia coli, Staphylococcus aureus, Salmonella typhi, and the fungus Cladosporium spherospermum. ZnO-CMC biofilms exhibited enhanced antimicrobial activity and greater resistance to degradation than CMC biofilms alone. These findings suggest that CMC synthesized from agricultural biomass such as wheat husk is a promising biodegradable material for food and pharmaceutical packaging. Additionally, the incorporation of ZnO nanoparticles further enhances its potential as an antimicrobial material for use in pharmaceutical applications.