ABSTRACT Fabrication of chemically crosslinked matrix system for controlled delivery of venlafaxine is the aim of study. AMPS (monomer) is used to chemically cross-link PVP (polymer) and Xanthan gum (Polymer) in the presence of ammonium per sulfate/sodium hydrogen sulfite. The effect of alteration in the amount of monomer, polymer, and crosslinker was evaluated. Swelling properties showed maximum swelling at pH 7.4 proved to indicate the pH-sensitive behavior. Kinetics modeling demonstrated the controlled release trend of venlafaxine in a fabricated gel. Toxicity studies confirmed the nontoxicity of developed gel. The controlled delivery of venlafaxine was effectively achieved by xanthan gum/PVP-co-poly (AMPS) hydrogels.