Objective: Tamarind seed polysaccharide (TSP) modifying to carboxymethyl tamarind seed kernel polysaccharide (CMTSP) could be potential polymer over synthetic one to target colon diseases. Ibuprofen was loaded in CMTSP to achieve colon targeted sustained action of pellets due to viscous nature of CMTSP. Methods: Ibuprofen loaded CMTSP pellets prepared by extrusion spheronization technique were optimized using three-level two-factor full factorial design. Results: Higher was the amount of CMTSP; better was the crushing strength of pellets, needed to target at the colon. in vitro dissolution test of the pellets at pH 1.2, 6.8 and 7.4 phosphate buffer showed drug release within 10 h. Further, the effect of enzyme induced in the colon portion of rat, in response to fed CMTSP and TSP, was carried out by performing dissolution study of pellets at 2 and 4% w/v of rat caecal matter in an anaerobic environment. The optimal calculated parameters were CMTSP and MCC, each at 300 mg, with highest crushing strength (23.6 N) and drug release (98%) within 9 h in presence of rat caecal content (4% w/v). Scanning electron microscopy revealed the spherical nature of pellets with rough surface and small pore openings for the drug release. Conclusion: Ibuprofen loaded pellets of CMTSP were successfully targeted at colon, due to increase in viscosity and decrease in swelling index of CMTSP than TSP.