The pathogenesis of periodontitis involves the interplay of microbiota present in the subgingival plaque and the host responses. Inflammation and destruction of periodontal tissues are considered to result from the response of a susceptible host to a microbial biofilm containing gram-negative pathogens. Antimicrobial peptides are important contributors to maintaining the balance between health and disease in this complex environment. These include several salivary antimicrobial peptides such as β-defensins expressed in the epithelium and LL-37 expressed in both epithelium and neutrophils. Among gram-negative bacteria implicated in periodontal diseases, Fusobacterium nucleatum, is one of the most interesting. This review will focus on expression, function, regulation and functional efficacy of antimicrobial peptides against F. nucleatum. We are looking for how the presence of F. nucleatum induces secretion of peptides which have an impact on host cells and modulate immune response.