Relationship between thyroid dysfunction and periodontal disease has been mediated through an immune response. Cytokines are implicated in the initiation, consequences of immune response and a crucial role in the pathogenesis of thyroid disease, directly target thyroid follicular cells; and in the development and progression of periodontitis. This study aimed to detect cytokines levels which known to be associated with periodontitis in serum and saliva, to test the hypothesis that hypothyroidism influences the levels of biomarkers of periodontitis. Samples were collected from sixty patients with hypothyroid age ranged (20-64) years, thirty of patients were without periodontitis (group I) and 30 with periodontal disease (II); moreover, 30 subjects considered as control (group III) with age (20-53) years. Detection of cytokines was performed by ELISA. The results showed a significant elevation in serum and salivary levels of IL-1β (P<0.001) among patients’ groups (I and II) as compared to group III, as well IL-1β increase significantly in group II (P<0.001) than in group I and also than group III. There are nonsignificant differences (P>0.05) in serum level of IL-6 and TNF-α and salivary levels of TNF-α among all study groups. Nevertheless, the salivary level of IL- 6 is increased significantly (P<0.05) in group II as compared with group I and group III, and their non-significant differences (P<0.05) between groups I and III. The present finding proposed that hypothyroidism might encourage periodontitis development; as well as serum and salivary levels of IL-1β, with salivary IL-6 may represent important biomarkers for the early detection of periodontitis in hypothyroid patients.