The study aims to extract and purify chitosan (CS) from the exoskeleton of crab (C. natator) and develop ibuprofen (IBU) encapsulated CS nanoparticles (IBU-CSNPs). Analysis of purified CS revealed characteristic functional and crystallinity peaks. Moreover, morphological analysis of prepared IBU-CSNPs showed uniform spherical shape with a size range of 40-100 nm whereas encapsulation efficiency (EE%) and loading capacity (LC%) were estimated to be 68.94 ± 1.61% and 28 ± 1.18% respectively. Further, in vitro release profile of IBU from IBU-CSNPs was observed to be in biphasic form with initial release up to 15 h followed by the sustained release in different test conditions. Further, the effects of purified CS on the viability of RAW264.7 cells exhibited no toxic effects in higher concentrations. Furthermore, fluorescein isothiocyanate (FITC) conjugated nanoparticles (FITC-IBU-CSNPs) were investigated on in vivo model of adult zebrafish for time-dependent circulation and accumulation of the drug through the nano-carrier system. It was observed that the drug diffusion from the nanoparticles was in a sustained manner throughout the gastrointestinal region which resulted in suppression of inflammation. Overall, this study provides an effective and facile process for preparing a crab CS-based nano-carrier system used for the delivery of IBU in vivo which may help in the curing of prolonged chronic inflammatory diseases. Moreover, it may also help to reduce adverse effects of these drugs in the gastrointestinal tract such as ulcers and bleeding.