The aim of the study was to synthesize and characterize a potential crosslinked polymeric system for oral targeted delivery of 5-Fluorouracil, a first-line anticancer agent in colorectal cancer. β-Cyclodextrin crosslinked with methacrylic acid (β-CD MAA) hydrogels were developed using free radical copolymerization in aqueous media. ATRFTIR spectra of β-CD MAA hydrogels confirmed the formation of a new crosslinked polymeric structure and SEM images revealed a porous network structure. Thermogravimetric analysis and differential scanning calorimetry (TGA & DSC) analyses clearly indicated high thermal stability of the developed new crosslinked polymer hydrogel structure. Physiochemical properties such as swelling index, gel fraction and porosity of hydrogels were measured. 5-Fluorouracil (5-FU), an antineoplastic agent, was incorporated as a model drug. Rapid swelling and drug release were observed at pH 7.4. However, the swelling index and 5-FU release remained very low at pH 1.2. This investigation demonstrated the strong site specific release potential of β-CD MAA hydrogels for colonic delivery of antineoplastic agent 5-FU.