Antimicrobial packaging is a promising form of active packaging that refers to the incorporation of antimicrobial agents into packaging systems with the aim to extend the product shelf life maintaining its quality and safety. In our work an antimicrobial active packaging based on poly(ethylene terephthalate) (PET) was prepared by sol–gel route, incorporating as antimicrobial agent lysozyme with the aim to obtain packaging films with controlled release properties. The fine tuning of the sol concentration and viscosity as well as the dip-coating extraction rate, allowed to deposit on the external surface of the PET support uniform coatings with controllable thickness at the sub-micron scale. FTIR microspectroscopic and tapping mode-Atomic Force Microscopy (TM-AFM) measurements were used to characterize the prepared coatings. The antimicrobial activity of the obtained surface modified films was tested on agar plates against Micrococcus lysodeikticus. Furthermore, the stability of the coating was evaluated in order to verify a possible migration of lysozyme to a liquid media (buffered solution at pH 6.2), due to a possible release from the plastic substrate. The quantitative determination of the released lysozyme in the buffered solution was performed by HPLC UV-DAD. Results show that the incorporation of lysozyme into the sol–gel modified PET do not lead to a loss of activity of the enzyme, and suggest a significant potential for the use of these packaging materials.