Oxidative stress is involved in many of the stages of tumorigenesis, and the administration of exogenous antioxidants seems to modulate them. Thus, it has been described that oleuropein and hydroxytyrosol exert important anti-cancer activities. We analyse in vivo the anti-tumor properties of both phenolic compounds in an animal model of glioma, and their effects on oxidative stress, enzymatic and non-enzymatic antioxidant defence systems and on several biochemical biomarkers. Hydroxytyrosol, but not oleuropein nor the mixture of both compounds, inhibits tumor growth through mechanisms that involve enzymatic and non-enzymatic antioxidant defences, as demonstrated by a decrease in lipid peroxidation and protein oxidation levels. Furthermore, hydroxytyrosol maintains the non-enzymatic antioxidants as in healthy animals, and positively modifies the enzymatic antioxidants. However, hydroxytyrosol probably acts not as an antioxidant, but through other mechanisms that only indirectly modify the redox status. Finally, these compounds yield few adverse effects related to changes in hepatic enzymes.