One of the most important functions of the oral fluid is to maintain oral homeostasis. In-office teeth whitening systems are able to change the mineral metabolism and the activity of a number of enzymes in the oral fluid, but there are conflicting data in publications about this. The aim of this study was to compare the effect of Opalescense Boost, ZOOM Advance POWER, and ZOOM Phillips White Speed, which contain different percentages of hydrogen peroxide, on the performance of oral fluid. After the procedure of whitening teeth with the studied in-office systems, the concentration of calcium in the oral fluid increased, and the activity of alkaline phosphatase decreased. Calcium levels returned to baseline values after 30 days, and alkaline phosphatase activity returned after 14 days. There was no significant difference in the changes in calcium concentration and alkaline phosphatase activity between different tooth whitening systems. Chemical teeth whitening with the Opalescense Boost system caused the largest change in the activity of superoxide dismutase in the oral fluid compared to the ZOOM Advance POWER and ZOOM Phillips White Speed photocatalytic teeth whitening systems. An increase in the activity of superoxide dismutase by +75.5% was shown immediately after the procedure of teeth whitening with the Opalescense Boost system, which indicated an increase in the power of antioxidant defense mechanisms. To assess the effectiveness and safety of using various whitening systems, it is possible to study the dynamics of the activity of superoxide dismutase, which reflects the processes of antioxidant protection of the oral cavity.