Background. Periodontitis is one of the most common dental diseases. It is generally accepted that concomitant diseases and syndromes significantly change physiological processes in the body, reduce its adaptive capabilities and treatment effectiveness, and can initiate or activate the pathological process in the periodontium. Psychosomatic disorders and stress are no less common. The excessive and prolonged action of stress factors can contribute to developing diseases. Currently, questions concerning the pathophysiological characteristics of changes in the processes of lipid peroxidation and antioxidant protection in the pathogenesis of periodontitis associated with stress remain unexplored. The purpose was to investigate the pathophysiological features of lipid peroxidation and antioxidant protection disorders in periodontal tissues with experimental periodontitis (EP) associated with immobilization stress (IS) and to evaluate the possibility of their pharmacological correction using thiocetam. Materials and methods. Biochemical studies were conducted on 88 male guinea pigs (males) with a body weight of 0.18–0.21 kg, who were fed a standard diet and were divided into five groups. The first group comprised intact animals (controls); the second group included animals with EP and was divided into three subgroups on the 3rd, 5th, and 15th days, respectively; the third group consisted of animals with IS in three subgroups; the fourth group comprised animals with combined EP and IS in three subgroups before treatment; and the fifth group included animals with EP and IS after the therapy with thiocetam, which was administered intramuscularly at a dose of 250 mg/kg once a day between the 6th and 15th days. Results. EP associated with IS at all stages of its development (3rd, 5th, 15th days) is accompanied by a gradual increase in the level of diene conjugates, malondialdehyde, a compensatory increase in superoxide dismutase and catalase activity on the 3rd day of the experiment, and subsequently by their significant decline on the 5th and 15th days, which indicated the development of oxidative stress. Thiocetam decreased lipid peroxidation products and increased the activity of these enzymes in periodontal tissues, which showed its antioxidant effect in EP and IS. Conclusions. The association between EP and IS resulted in the enhancement of lipid peroxidation processes against the backdrop of a decreased antioxidant protection in periodontal tissues, particularly on the 5th and 15th days of the experiment, compared to the control group, indicating the presence of oxidative stress. The administration of thiocetam had the antioxidant effect (a reduction in the concentration of diene conjugates, malondialdehyde, an increase in superoxide dismutase, and catalase activity in periodontal tissues) under the conditions of EP associated with IS compared to a group of animals without any treatment.