Objectives <p>This paper aims to review the immunopathogenesis of Diabetes-associated periodontitis (DPD) and to propose a description of the research progress of drugs with potential clinical value from an immunotherapeutic perspective.</p> Materials and methods <p>A comprehensive literature search was conducted in PubMed, MEDLINE, Embase, Web of Science, Scopus and the Cochrane Library. Inclusion criteria were studies on the association between diabetes and periodontitis using the Boolean operator “AND” for association between diabetes and periodontitis, with no time or language restrictions. Search terms included diabetes mellitus, periodontitis, immunopathogenesis, specific immunity, non-specific immunity, flora, estrogen, pharmacological treatment, immunotherapy.</p> Results <p>Alterations in the subgingival flora environment in a hyperglycemic environment elicit an immune response. Overactivity/suppression of nonspecific immune cells and impaired cellular defenses trigger specific immune responses. Epigenetics as well as female hormones also play a role. There is already a small amount of clinical evidence for the role of metronidazole, subantimicrobial doses of doxycycline, minocycline hydrochloride, and metformin in the treatment of DPD. Some preclinical studies have also accumulated experimental evidence for the improved effects of vitamin D3 and other drugs on DPD.</p> Conclusions <p>The development of diabetic periodontitis is immunologically linked to a state of immune imbalance and therefore holds great promise for the use of immunotherapeutic drugs.</p> Clinical significance <p>Immunotherapy with drugs along with periodontal nonsurgical treatment could provide ideas for DPD treatment based on the immunopathogenesis of DPD.</p>