Abstract In order to solve the problem of bacterial resistance, increase the antibacterial performance and delay the aging of paper, the berberine modified trimethoprim carboxymethyl cellulose was prepared using trimethoprimethylate carboxymethyl cellulose as raw material and trimethoprimethylate lactate (TMP) as antibacterial modifier by Schiff Base reaction. At the same time, berberine (BBR) was used as graft monomer to prepare a multifunctional protective solution integrating strengthening, antibacterial and good biocompatibility. The optimal process conditions were determined by single factor experiment and response surface method. The structure and properties of the product were characterized by FT-IR, XRD, TG and SEM and the antibacterial properties were evaluated by AGAR disk diffusion method. The results showed that when the mass ratio of dialdehyde carboxymethyl cellulose and modified berberine was 7:15, reaction temperature was 40 °C, and pH was 6.0, the optimum synthetic conditions was obtained. And the minimum inhibitory concentration of the product against Staphylococcus aureus and Escherichia coli were 0.2 mg/mL, minimum diameter of antibacterial zone of 6.7 mm and 7.1 mm, respectively, with good antibacterial effect. This paper lays a foundation for further research on the safe and effective antiquities antibacterial agent, and provides a reference for its further development in paper protection.