Introduction: The immune system has been used to mediate the link between periodontal disease and the endocrine system, particularly thyroid dysfunction. Osteoprotegerin, a dimeric glycoprotein, its structure similar to receptor activator of nuclear factor kappa-b is generated and secreted by osteoblasts and considered as a member of the TNF family. To prevent RANK from contacting RANKL, OPG functions as a "false target." OPG is necessary for preventing osteoclast activation and development; as a result, bone resorption will stop. Objective: To demonstrate the salivary level of OPG in hypothyroidism and periodontitis patients in comparison to healthy controls. Patients and Method: Saliva samples were taken from 90 subjects ranging in age from (22-65) years, 50 of whom were hypothyroid patients (25 participants with periodontitis and systemically healthy; 25 participants with hypothyroidism and a healthy periodontium, 25 participants with hypothyroidism and periodontitis, and 15 individuals systemically healthy with healthy periodontium, which serve as the control group. OPG in saliva was discovered using ELISA. Result: According to the current findings, the levels of salivary OPG were significantly low in the disease group (periodontitis group, hypothyroid patient group with and without periodontitis) than in the control group. In addition, salivary levels of OPG were significantly lower in hypothyroidism with the periodontitis group in comparison to the periodontitis group. Conclusion: OPG has a protective role in disease processes, in which the level of OPG decreased in all diseases group and increase in health. Hypothyroidism affects the level of salivary OPG.