The present work deals with the preparation, characterization and evaluation of glutaraldehyde cross-linked chitosan-tamarind seed polysaccharide (TSP) interpenetrating polymeric network (IPN) microparticles for prolonged aceclofenac release. The drug entrapment efficiency of these microparticles was found 85.84 ± 1.75 to 91.97 ± 1.30% and their average particle sizes were ranged from 490.55 ± 23.24 to 621.60 ± 53.57 μm. These chitosan-TSP IPN microparticles were characterized by FTIR, DSC, and SEM analyses. The in vitro drug release from these aceclofenac-loaded chitosan-TSP IPN microparticles showed sustained release of aceclofenac over 8 h and followed the Korsmeyer-Peppas model (R2 = 0.9809–0.9828) with anomalous (non-Fickian) diffusion drug release mechanism. The in vivo studies exhibited sustained anti-inflammatory activity in carrageenan-induced rats over prolonged period after oral administration of these newly developed aceclofenac-loaded IPN microparticles.