Recently, bioactive dietary fibers (DFs) have been explored for various benefits to human health because of their therapeutic activities. Role of DF psyllium (arabinoxylan (Ax)) has been established for curing colon cancer. Herein, methotrexate (MXT), an anti-neoplastic agent, was impregnated into network hydrogels developed from DF psyllium, through graft copolymerization reactions for its sustained colon-specific drug delivery (DD). Copolymers were characterized through SEM, AFM, FTIR, C13-NMR and TGA analysis. Smart hydrogels demonstrated antioxidant (39.40 ± 0.78% free radical scavenging in the DPPH assay), biocompatible (1.16 ± 0.22% hemolysis value in blood-polymer interactions), and mucoadhesive (7.0 ± 0.1 mN detachment force from the mucous membrane) properties. Sustained diffusion of MXT in colonic conditions occurred with a Fickian mechanism, and release profile obeyed the Korsmeyer-Peppas kinetic model. Overall, findings suggested the suitability of DF psyllium-based DD carriers for colon with enhanced potential.