In the present work, amoxicillin drug-loaded films of poly (vinyl alcohol)-g-poly (acrylamide) of varying compositions were prepared by graft copolymerization method. The as-prepared drug-loaded grafted hydrogels were characterized by various analytical techniques such as Fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, and X-ray diffraction analysis, respectively. The grafted hydrogels were investigated for their water intake behavior under varying experimental conditions of their chemical composition, pH and temperature of the swelling bath, and simulated biological fluids. The water sorption data of hydrogels were used to calculate network parameters of the grafted hydrogel such as average molecular weight between crosslinks (M-c), crosslink density (V-e), number of elastically effective chains (q(e)), swelling exponent (n), and diffusion constant (D), respectively. The swelling controlled drug release behavior of amoxicillin loaded hydrogel was investigated under in vitro conditions, and the influence of various factors such as chemical composition of grafted hydrogel, percent loading of drug (amoxicillin), pH and temperature of the release media was studied on the release profiles of the drug. The amoxicillin loaded grafted hydrogels were also examined for their antibacterial activity against gram-negative bacteria.