High-density polyethylene HDPE is a highly polluting plastic, and its reuse, reprocessing and modification are subjects of current research to mitigate environmental pollution. In recent times, it has been modified for specialized purposes as a harmless and resistant polymer. The present work details the modification of HDPE (obtained from Bonafont, Coke, and Gatorade caps) with the monomer 4-vinylpyridine (4VP) via radiation-induced grafting copolymerization initiated by gamma rays from a Co-60 source and with the subsequent Ag(I) loading using the reagent AgNO3 in aqueous medium. Poly(4VP) is widely used to retain metals and manufacture pH-responsive polymers, while Ag(I) is a recognized bactericide harmless to humans at therapeutic concentrations; therefore, both poly4VP and Ag(I) can work in a synergistic system against pathologic bacteria as is here proposed. We advance a favorable antimicrobial activity of the Ag-loaded graft copolymers evaluated in vitro with Kirby-Bauer tests against Pseudomonas aeruginosa and Staphylococcus aureus. Additionally, FTIR-ATR, TGA, contact angle, swelling, and pH response were carried out to complete the characterization.