The risk of infections in chronic wounds represents a serious issue, particularly in aged people and in patients affected by diseases such as diabetes and obesity. Moreover, the growing resistance demonstrated by many bacterial strains has significantly reduced the therapeutic options for clinicians and has become a great challenge for the researchers in the definition of novel approaches that promote the wound healing process and reduce the healing time. Tissue engineering approaches based on biomaterials and three-dimensional scaffolds have demonstrated huge potential in supporting cell proliferation; among them, Bombyx mori-derived silk fibroin is a very appealing possibility for the development of devices with regenerative properties for wound healing applications. However, due to the high risk of infections in chronic wounds, an antibacterial treatment is also strongly encouraged for preventing bacterial proliferation at the wound site. In this work, to develop a device with regenerative and antibacterial properties, antibacterial silver coatings were deposited onto silk fibroin scaffolds, and the effect of the treatment in terms of chemical–physical and microbiological properties was investigated. The results demonstrated that the silver treatment improved the mechanical properties of the protein scaffold and provided good antibacterial efficacy against representative bacterial strains in wound infection, namely Escherichia coli and antibiotic-resistant Pseudomonas aeruginosa.