Multiple anti-inflammatory medications have helped treat inflammatory bowel disease (IBD). However, oral administration has minimal absorption and systemic side effects. This study aims to investigate the potential of encapsulating anti-inflammatory drug celecoxib (Cele) within microbeads for the treatment of IBD. Microbeads were formed by cross-linking carboxymethyl chitosan (CMCs) with sodium alginate (Alg) through the ionic gelation method and optimized through response surface methodology. Additionally, the study revealed a mucoadhesivity value of 59.32 +/- 0.74 % for the optimized microbead system. The drug release study demonstrated the sustained release of Cele CMCs/Alg microbeads upto 24 h compared to quick release of the free drug. The results of the cell viability assay indicated that the Cele-Alg/CMCs microbeads exhibited a non-toxic nature within the concentration range of 100-250 muM. A significant decrease in nitric oxide (NO) generation (61.14 +/- 3.67 %) was seen in HCT-116 cells stimulated with lipopolysaccharide (LPS) upon treatment with Cele-250(muM)/CMCs/Alg microbeads. The results of the reactive oxygen species and wound healing assay suggest that Cele-250(muM)/CMCs/Alg microbeads had improved anti-inflammatory characteristics comparable to those of free drug treatment. The western blot analysis demonstrated that the microbeads composed of CMCs/Alg-Cele possess the capacity to inhibit the expression of COX-2 in vitro supressing inflammation.