© 2016, Springer-Verlag Berlin Heidelberg.Objective: The purpose of this study was to determine the effect of non-surgical periodontal treatment on markers of oxidative stress in saliva and serum in patients with chronic periodontitis. Materials and methods: In total, 25 patients, who were diagnosed with generalized chronic periodontitis (11 females and 14 males), and 26 systemically and periodontally healthy individuals (15 females and 11 males) were included. The plaque index (PI), gingival index (GI), probing pocket depth (PPD), attachment loss (AL), gingival recession (GR), and bleeding on probing (BOP) were recorded at baseline and 6 weeks later. Malondialdehyde (MDA), 8-hydroxydeoxyguanosine (8-OHdG), and 4-hydroxy-2-nonenal (4-HNE) were assessed in saliva and serum samples before and after the non-surgical treatment by enzyme-linked immune sorbent assay (ELISA). Results: In the group with chronic periodontitis, all clinical parameters were significantly higher compared to the control group at baseline (p < 0.001). Periodontal treatment reduced plaque, gingival inflammation, and pocket depth significantly (p < 0.001). At baseline, salivary 8-OHdG was significantly higher in chronic periodontitis (p < 0.001) and reduced significantly subsequent to the periodontal treatment (p < 0.001). Salivary MDA and serum 4-HNE were significantly higher in the patients with periodontitis compared to the control group (p < 0.001). Periodontal treatment did not significantly change the levels of 4-HNE and salivary MDA (p = 0.503, p = 0.093). Conclusions: Salivary 8-OHdG and MDA may be associated with local impact of periodontal disease, while 4-HNE may be associated with systemic impact of chronic periodontitis. Clinical relevance: Clinical intervention in periodontitis may be beneficial for periodontitis patients’ systemic oxidative stress control, and using lipidic agents for the use of anti-inflammatory/pro-resolving processes for blocking the actions of arachidonic acid cascade can enable some late therapeutic strategies in order to lead oxidative stress-induced inflammation.