This research describes the preparation of ornidazole (ORZ) polymeric nanoparticles by using chitosan as polymer for colon-specific delivery. The polymeric nanoparticles were prepared by the ionic gelation method. The nanoparticles were evaluated for their in vitro drug release properties. Scanning electron microscopy was used for morphology observation. The nanoparticles exhibited mucoadhesive properties, which diminished with increasing drug content. The nanoparticles with a particle size range between 180 and 280 nm exhibited excellent mucoadhesive properties. The results shown that the formulated nanoparticles have succeeded in controlling the release of (ORZ) over a 14-hr period. In conclusion, the release of ORZ was found to be dependent upon the composition of the nanoparticles, the ratio of the components and possible particle size, as well as bioadhesive ability. © 2022 Elsevier B.V., All rights reserved.