In our previous studies, we have illustrated that sage essential oil has a good protective effect against oxidative stress that is induced by hydrogen peroxide on the phenotypic parameters of the protozoan Tetrahymena, given that this protection is characterized by a significant improvement in cell growth and normal cell morphology. On the whole, this work includes studying the intracellular effect of the essential oil of sage on the specific activity of certain antioxidant enzymes such as Catalase (CAT) and Superoxide Dismutase (SOD), lipid peroxidation rate (MDA) and specific activity of the GAPDH biomarker in the model organism Tetrahymena thermophila. As a result, our studies have shown that H2O2 significantly decreases the activities of CAT SOD, GAPDH and significantly increases the rate of MDA. On the other hand, in the presence of sage oil, there is a very significant increase in the activities of the CAT and the GAPDH, a restoration of the activity of the SOD and the rate of MDA. These results confirm that sage oil has a protective effect against oxidative stress by trapping Reactive Oxygen Species (ROS) released by hydrogen peroxide and enhancing the activity of intracellular antioxidant enzymes. Therefore, this oil can be a good alternative for the prevention of oxidative stress-related diseases.