Guar Gum has been evaluated for its importance in the food and pharmaceutical industry. A blended biopolymeric hydrogel was prepared by solution casting technique using guar gum (GG), chitosan (CS), polyvinyl alcohol (PVA), chemically crosslinked with tetra orthosilicate (TEOS), and impregnated with methotrexate (MTX) to assess its drug carrying capacity against colon cancer (HCT-116). The surfacemorphology, chemical bonding, hydrophilicity, and water absorbing capacity were analyzed by atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FTIR), contact angle measurements, and swelling properties in variable conditions. Furthermore, degradation, drug release kinetics, hemocompatibility, and cytotoxicity of MTX-loaded hydrogel were tested. The release of MTX from the GG/CS/PVA biopolymeric blend occurred in a sustained manner. Results displayed that in 7h 25min duration, 96% of the drug was released in phosphate buffer saline (PBS) at pH 7.4. These blends were non-hemolytic and antiproliferative against HCT-116. Furthermore, the MTT assay has revealed that MTX-loaded hydrogel had prominently decreased the cell viability (with IC50 11.7µg/ml) as compared to free MTX (with IC50 21.57µg/ml). Hence, these results suggest that guar gum based hydrogels are potential biomaterials for colon cancer treatment.