Indolicidin-coated silver nanoparticles could be used as platforms in the dental field as oral disease preventive drug. Furthermore, nanomaterials could prevent oral cancers and balance oral health care.

(1) Background: In dentistry, silver nanoparticles (AgNPs) have progressively earned great interest as antimicrobial drugs and are widely used in several biomedical fields. Recent progress in the analysis of complex bacterial communities has demonstrated the richness of the oral microbiota and the presence of numerous previously unexplained strains. Several efforts have been dedicated to the investigation of antimicrobial peptides (AMPs). Those peptides are a widespread group of small peptides against invading microbes. We report the production of a hybrid molecule composed of AgNPs and indolicidin, a well-known antibacterial peptide. (2) Methods: Spectroscopy and microscopy were used to analyze the optical features and to determine the size of the generated AgNPs. The AgNP antibacterial activity was evaluated versus oral Gram-positive and Gram-negative bacteria. (3) Results: The coated nanoparticles’ antibacterial activity strongly inhibited the growth of microorganisms, with very low minimum inhibitory concentration (MIC) values in the range of 5–12.5 μg/mL. We hypothesize that this effect depended on the specific characteristics of the metal surface coated with indolicidin. The second result was that the coated nanoparticles observed cellular toxicity, was lower with respect to the toxicity of peptide and the naked AgNPs when used individually. (4) New investigations regarding antimicrobial effect of AgNPs coated with AMPs in oral infections are an urgent task.