The nanocomposite hydrogels were prepared by dispersing of the nanopomegranate seed particles into poly(vinyl alcohol)/poly(acrylic acid) blend matrix in an aqueous medium by the solvent casting method. These hydrogels were characterized using scanning electron microscopy, Fourier transform infrared spectra, differential scanning calorimetry, and optical contact angle instruments. The nanopomegranate seed, blend, and hydrogel nanocomposites were tested for microbial activity. In addition, cytocompatibilities of these blend and hydrogel nanocomposites/composites were tested on human lymphocyte with in vitro MTS cell viability assays. Fourier transform infrared spectra revealed that esterification reaction took place among functional groups in the structure of poly(vinyl alcohol) and poly(acrylic acid). The hydrophilic properties of all hydrogels decreased with increasing nanopomegranate seed content. The mean diameters of the nanopomegranate seed particles were about 88 nm. Nanopomegranate seed particles demonstrated antibacterial properties against gram-positive bacteria, Staphylococcus aureus, and gram-negative bacteria, Escherichia coli. The lymphocyte viabilities increased after addition of nanopomegranate seeds into the polymer blend. The swelling behavior of blend and hydrogels was dependent on the cross-linking density created by the reaction between poly(vinyl alcohol)/poly(acrylic acid) blend and nanopomegranate seed. Scanning electron microscopy images were highly consistent with Fourier transform infrared spectra, differential scanning calorimetry, and antibacterial activity results.