Oxidative stress takes part in the pathomechanisms of many diseases, including oral disorders. The imbalance between oxidative and antioxidative processes may lead to periodontitis, osteitis, or oral cancers. Furthermore, many chemotherapeutics, e.g., metronidazole (MTZ), may also cause toxic reactions and affect oxidative reactions. The research focused on MTZ influence on oxidative destruction in the parotid and submandibular gland tissue in animal experimental model. Therefore, the concentrations of enzymatic and nonenzymatic markers of oxidative stress were measured in these two rat glands in the control and experimental MTZ-treated groups. The material for analysis included parotid and submandibular glands of male Wistar rats, which were treated with metronidazole for 7 days by gastric tube in a dose of 100 mg/kg b.w. On day 8, the material was obtained and frozen in temp. -80°C. Then, the following seven enzymatic and nonenzymatic parameters were measured: GPx, TOS, TAS, SOD, LPO, CAT, and GSH. The data were analysed using Statistica 10.0. Metronidazole treatment in the experimental model showed an increase in LPO, TOS, and TOS/TAS and a decrease in CAT, SOD, GPx, and TAS. The conclusions of this research were made. Metronidazole treatment in a dose of 100 mg/kg b.w. caused imbalance between oxidative and antioxidative reactions in the rat parotid and submandibular glands. An increase was observed in LPO, TOS, and TOS/TAS in both glands exposed to metronidazole. Decreased activity of CAT, SOD, GPx, and TAS was noted, which indicates attenuation of the gland antioxidative protective barrier.