Periodontitis is a polymicrobial infection characterized by a destructive inflammatory process that leads to the loss of tooth-supporting tissues, including the periodontal ligament and alveolar bone. Attachment loss continues when the PDL is progressively damaged and since the PDL anchors the tooth to the alveolar bone, bone loss follows resulting from host-mediated enzyme and oxygen radical release. In addition to the direct bone destruction by immune cells, the osteoclast-osteoblast balance can become modified, favouring osteoclastic bone resorption. This can result from increased osteoclastogenesis which is primarily stimulated by receptor activator of NFκB ligand (RANKL) expressed on the surface of osteoblasts and from activated T lymphocytes and many other cells.NAC as anti-oxidant drug is a safe drug in human used for many years as a mucolytic agent. Previous studies have suggested that NAC suppressed periodontal inflammation and alveolar bone loss in periodontal disease in an experimental periodontitis model in rats. The aim of this study was to evaluate the effect of N-Acetylcysteine (NAC) anti-oxidant drug on the soluble receptor activator nuclear factor kappa-B ligand (sRANKL) level in gingival crevicular fluid in patients having moderate to advance chronic periodontitis treated by non- surgical and surgical periodontal treatment. Materials and Methods: Twenty seven subjects (10 males, 17 females) were participating in the study. They were divided into 3 groups, group I included 9 patients suffering from chronic periodontitis treated with surgical and non-surgical periodontal therapy with adjunctive 600mg NAC treatment, group II included 9 patients suffering from chronic periodontitis treated with surgical and non-surgical periodontal therapy without adjunctive NAC treatment and group III that included 9 periodontally healthy individuals as control group. In chronic periodontitis patients, Clinical parameters including PD, CAL, GI and PI were obtained at baseline before initial periodontal treatment, one month, 3 months and seven months after periodontal treatment. The gingival crevicular fluid (GCF) samples were collected from chronic periodontitis patients groups (group I and II) for assessment of sRANKL level at baseline before initial periodontal treatment, one month, 3 months and seven months after periodontal treatment. sRANKL was measured in the GCF samples by using Enzyme- linked Immunosorbent Assay (ELIZA) technique. The radiographic bone densities were assessed at baseline and 7 months after periodontal treatment in chronic periodontitis groups. Results: The clinical parameters of the present study showed statistically significant difference in PPD at 3 months in treated sites of chronic periodontitis groups with non-surgical or surgical treatment with adjunctive NAC when compared to chronic periodontitis groups with non-surgical or surgical treatment without adjunctive NAC. The results of immunoassay reveled that the GCF level of sRANKL showed statistically significant difference between control and both periodontitis groups. There was statistically significant reduction in the GCF levels of sRANKL at 1 and 3months after non-surgical treatment in both chronic periodontitis groups. The results also showed that there was no statistically significant difference in the GCF levels of sRANKL between both chronic periodontitis groups either with the non-surgical or surgical treatment. Conclusion: The results obtained from the present study revealed that GCF level of sRANKL was significantly decreased after non-surgical periodontal treatment in 1and 3months after completion of treatment either with or without NAC. The adjunctive NAC treatment induced more significant reduction in PPD during the period of administration.