The Present study deals with synthesis of PVC/ABS/ZnO nanocomposites with Zinc oxide nanoparticles of particle size less than 50 nm by sonication and solution casting techniques. After characterization, such nanocomposite materials were subjected to thermal study, antibiofilm, antibacterial and antioxidant screening. Nanocomposites films showed higher thermal stability than pure polymer matrix loaded with different ZnO-Nps concentration with homogeneous distribution. Antibacterial studies were carried out against selected gram-positive bacteria: Staphylococcus aureus and gram-negative bacteria: Pseudomonas aeruginosa. Selective antibiofilm activity was studied against Staphylococcus aureus and Pseudomonas aeruginosa, which showed a higher to lower activity as a model pathogenic strains (~93 and ~89 at 160 μg/ml concentration, respectively), while free radical scavenging capacity was assessed by DPPH, ABTH·+ and FRAP methods. PVC/ABS/ZnO nanocomposite showed larger zones of inhibition and higher antibiofilm and antioxidant activity than PVC/ABS polymer matrix. PVC/ABS/ZnO nanocomposite showed enhanced thermal stability and biological properties that qualify them for different biomedical and industrial applications.