In the present research the antimicrobial activity of two active packaging materials on the spoilage microbiota of fresh salmon fillets was tested. A PET-coated film (PET: Polyethylene Terephthalate) containing lysozyme and lactoferrin was tested in parallel with a carvacrol-coextruded multilayer film. Salmon fillet samples were stored up to four days at 0 and 5 °C, comparatively. The carvacrol multilayer film was found effective in preventing mesophiles and psychrotrophs at shorter storage time and at lower temperature (4.0 compared to 5.0 log CFU/g in the control sample—CFU: Colony Forming Units). Lysozyme/lactoferrin-coated PET was instead efficient in decreasing H2S-producing bacteria at longer storage time and higher temperature (2.7 instead of 4.7 log CFU/g in the control sample). Even if is not intended as a way to “clean” a contaminated food product, an active package solution can indeed contribute to reducing the microbial population in food items, thus lowering the risk of food-related diseases.