Periodontitis is a multifactorial chronic inflammatory disease that affects tooth-supporting soft/hard tissues of the dentition. The dental plaque biofilm is considered as a primary etiological factor in susceptible patients; however, other factors contribute to progression, such as diabetes and smoking. Current management utilizes mechanical biofilm removal as the gold standard of treatment. Antibacterial agents might be indicated in certain conditions as an adjunct to this mechanical approach. However, in view of the growing concern about bacterial resistance, alternative approaches have been investigated. Currently, a range of antimicrobial agents and protocols have been used in clinical management, but these remain largely non-validated. This review aimed to evaluate the efficacy of adjunctive antibiotic use in periodontal management and to compare them to recently suggested alternatives. Evidence from in vitro, observational and clinical trial studies suggests efficacy in the use of adjunctive antimicrobials in patients with grade C periodontitis of young age or where the associated risk factors are inconsistent with the amount of bone loss present. Meanwhile, alternative approaches such as photodynamic therapy, bacteriophage therapy and probiotics showed limited supportive evidence, and more studies are warranted to validate their efficiency.