The purpose of the present study was to fabricate polymeric nanoparticles as drug carriers for encapsulated curcumin with enhanced anti-colorectal cancer applications. Nanoparticles were formulated from chitosan and gum arabic, natural polysaccharides, via an emulsification solvent diffusion method. The formation of curcumin nanoparticles was confirmed by Fourier transform infrared spectroscopy and differential scanning calorimeter. The results show that curcumin was entrapped in carriers with +48 mV, 136 nm size, and high encapsulation efficiency (95%). Based on an in vitro release study, we inferred that curcumin nanoparticles could tolerate hydrolysis due to gastric juice or small intestinal enzymes, and therefore, it should reach the colon largely intact. In addition, curcumin nanoparticles had higher anti-colorectal cancer properties than free curcumin due to greater cellular uptake. Therefore, we concluded that curcumin was successfully encapsulated in chitosan-gum arabic nanoparticles with superior anti-colorectal cancer activity.