Context: Ursodeoxycholic acid (UDCA) exerts dose-dependent chemoprevention in colonic inflammation. Polycationic UDCA nanoparticles (UNPs) are envisaged for solubility enhancement and site directed drug delivery. Objective: The objective was to study the ameliorative efficacy of UNPs through localized delivery of the drug. Methods: UNPs were prepared through nanoprecipitation technique. Particle size, morphology, in vitro drug release and in vivo protective efficacy in inflammatory bowel disease (IBD) of these nanoparticles were studied. Results and Discussion: The average particle size was around 100 nm, and the average drug encapsulation was about 99%. In vitro drug release study shows optimal drug release in simulated colonic fluid. The lowering of tissue nitric oxide, malondialdehyde, myeloperoxidase and histology of the colon tissue supported the protective efficacy of the nanoparticles. Conclusion: This study presents the improved efficacy of UNPs in animal model of IBD due to complete release of drug at the desired site of action.