Thanks to its peculiar interactions with biological molecules and structures, metallic silver in the form of silver nanoparticles achieved a remarkable comeback as a potential antimicrobial agent. The antimicrobial use of silver nanoparticles is of clinical importance, as several pathogenic microorganisms developed resistance against various conventional drug treatments. Hence, given the extensive efficiency of silver nanoparticles against drug-sensitive and drug-resistant pathogens, their therapeutic implications were demonstrated in multiple medical applications, such as silver-based dressings, silver-coated biomedical devices and silver-containing nanogels. Bacterial strains possess an intrinsic ability to form well-organized microbial communities, capable of developing adaptive mechanisms to environmental aggression and self-protective pathways against antibiotics. The formation of these mono- or poly-microbial colonies, called biofilms, is closely related with the occurrence of infectious processes which result in severe and chronic pathologies. Therefore, substantial efforts were oriented to the development of new protective coatings for biomedical surfaces, capable of sustaining the physiological processes within human-derived normal cells and to disrupt the microbial contamination and colonization stages. Nanostructured materials based on polylactic acid and silver nanoparticles are herein proposed as bioactive coatings able to prevent the formation of microbial biofilms on biomedical relevant surfaces.