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Abstract This systematic review aimed to answer the focused question: “What are the benefits of subgingival periodontal therapy on blood hematological and biochemical index, biomarkers of inflammation and oxidative stress, quality of life, and periodontal pathogen counts in patients with obesity and periodontitis?”. A systematic literature search was performed in six databases: PubMed, Embase, LILACS, Web of Science, Cochrane and SCOPUS and other sources, and a manual search was conducted as well. Inclusion criteria were randomized and non-randomized clinical trials, and before-and-after studies on patients with obesity subjected to periodontal therapy. The results were synthesized qualitatively. Risk of bias within studies was assessed using RoB 2 and ROBINS-I tools. The certainty of evidence was evaluated following the GRADE approach. Three randomized controlled trials and 15 before-and-after studies were included. Randomized controlled trials were considered to have a low risk of bias, as compared to before-and-after studies assessed as having low, serious, and critical risks of bias. Non-surgical periodontal therapy plus azithromycin, chlorhexidine, and cetylpyridinium chloride reduced blood pressure and decreased serum levels of HbA1c, hsCRP, IL-1β, and TNF-α. Salivary resistin level also decreased in patients with obesity and periodontitis after therapy and chlorhexidine mouth rinse. Before-and-after data suggest an improvement in total cholesterol, LDL, triglycerides, insulin resistance, C3, GCF levels of TNF-α, chemerin, vaspin, omentin-1, visfatin, 8-OHdG, and periodontal pathogen counts after therapy. question What index stress life periodontitis. . periodontitis?” databases PubMed Embase LILACS Science sources well nonrandomized non beforeandafter before qualitatively ROBINSI ROBINS I tools approach 1 included serious Nonsurgical Non surgical azithromycin HbA1c HbAc HbA c hsCRP IL1β, IL1β ILβ IL 1β, 1β β IL-1β TNFα. TNFα TNF α. α TNF-α rinse Beforeandafter Before cholesterol LDL triglycerides resistance C3 C TNFα, α, chemerin vaspin omentin1, omentin1 omentin 1, omentin-1 visfatin 8OHdG, 8OHdG OHdG 8 OHdG, 8-OHdG periodontitis? omentin-