Periodontitis is a chronic inflammatory disease that affects the supporting tissues of the periodontium. Comorbidity in patients with periodontitis with rheumatoid arthritis and psoriasis has been documented. In immunopathogenesis, it has been described that interleukin 17 participates in periodontitis and autoimmune diseases. In this regard, interleukin 17 induces the expression of β-defensin-2, an antimicrobial peptide with a proinflammatory effect. Currently, it is not known how periodontal therapy impacts the production of interleukin 17 and β-defensin-2. This is the first case report exploring the modification of interleukin 17/β-defensin-2 in a patient with periodontitis or autoimmunity, showing the importance and effect of non-surgical therapy on modifications of the immune response at the molecular level. The aim of this work is to evaluate the clinical improvement and the levels of interleukin 17/β-defensin-2 in saliva before and after periodontal treatment in a patient with periodontitis, rheumatoid arthritis, and psoriasis. We present the case of a 51-year-old male patient with a history of psoriasis and rheumatoid arthritis. On periodontal examination, he presented with periodontal pockets greater than 5 mm in 19 periodontal sites, with 100% bleeding on probing, and tooth mobility grades II and III in most of the dental organ. Subgingival instrumentation and oral hygiene instructions were performed. The patient showed favorable progress, with a reduction in periodontal pocket depth, bleeding on probing, and tooth mobility. Interleukin 17 levels were higher and β-defensin-2 levels were lower post-treatment. Non-surgical treatment decreased the inflammatory activity of periodontal disease, which led to increased interleukin 17 and decreased β-defensin-2 in saliva samples. The decrease in β-defensin-2 suggests its usefulness as a marker of inflammatory activity in periodontal disease.