Periodontitis is a chronic inflammatory disease that results from a complex polymicrobial infection. The purpose of this review was to assess the efficacy of systemic administered antibiotics as an adjuvant to full mouth scaling and root planing with antiseptics (full mouth disinfection) and without the use of antiseptics in conjunction with systemic antibiotics in the treatment of chronic periodontitis. The following systemic review was conducted in agreement with the recommendations of the Cochrane Collaboration and the principles of the PRISMA (Preferred Reporting Items for the Systemic Reviews and Meta Analyses statement). The search resulted in 31 studies. Only 6 studies fulfilled the inclusion criteria and were eligible to be included in this systemic review. Further, long term randomised control trials with careful case selection of specific treatment protocols as well as standardised regimens for antibiotic use is required to obtain sufficient scientific evidence based treatment clinical guidelines for adjuvant use of systemic antibiotics with full mouth scaling and root planing and full mouth disinfection in treatment of chronic periodontitis.