Sequential interpenetrating polymer networks (IPN) hydrogels based on konjac glucomannan (KGM) and poly(methacrylic acid) (PMAA) were prepared by immersion of a solution of methacrylic acid (MAA) monomer with cross-linker N,N′-methylenebisacrylamide (MBAAm) and initiating into a pre-fabricated dried KGM gel. Polymerization and cross-linking of MAA inside the KGM network resulted in a novel biodegradable pH-sensitive IPN hydrogel. The studies on the swelling behavior of IPN hydrogels reveal their sensitive response to environment pH value. It was possible to modulate the degree of swelling of the IPN gels by changing the KGM/PMAA ratio and the cross-linking density of the PMAA component. The KGM component in the IPN can be degraded by β-glycosidase Mannaway25L. In vitro drug release behavior of IPN hydrogels were investigated under different environments using model drugs 5-fluorouracil. The results suggested that such an IPN hydrogel can be exploited as carrier candidate for colon-specific drug delivery.