Curcumin is a polyphenolic molecule with antibacterial, antioxidant, anti-inflammatory, and antimicrobial properties. This study aimed to prepare nanocurcumin by encapsulating in biopolymers to improve its stability, bioavailability, water-solubility, antibacterial efficiency against methicillin-resistant . Three effective variables of curcumin concentration, polymer concentration, and water volume on curcumin-loaded polymer nanoparticles, were optimized. The average size of polyacrylic acid (PAA), polyvinyl alcohol (PVA), and polyethyleneimine (PEI) nanoparticles were obtained 75.2, 77.1, 86.4 nm, respectively. The nanoparticles had a spherical shape, a smooth and uniform surface morphology. The MIC of PAA, PVA, and PEI nanoparticles was 0.480, 0.390, and 0.340 mg/mL, respectively and the MIC of PAA, PVA, and PEI combined with methicillin was 0.330, 0.260, and 0.200 mg/mL, respectively. According to the results, curcumin-loaded PEI nanoparticles had the highest inhibitory effect against methicillin-resistant among the synthesized nanoparticles. The results showed that solvent volume, polymer concentration and curcumin concentration had a significant effect on particle size. The inhibitory properties of curcumin nanoparticles significantly increased due to the smaller particle size and increased penetration into the bacterium. Curcumin-loaded nanoparticles can be promising drug carriers for the treatment of infections, cancer, and other diseases.