The aim of this investigation was to examine the effect of aerobic exercise (AE) on uric acid (UA), total antioxidant activity (TAA), oxidative stress (OS) and nitrite a stable nitric oxide (NO) metabolite in saliva from persons with Down syndrome (DS). Stimulated saliva was sampled from 12 participants 1 hour before and immediately after a 1,600-meter walking test. Uric acid (UA) was assayed by enzymatic method, TAA by ABTS method, lipid hydroperoxides (OS marker) by the ferrous iron/xylenol orange (FOX) method and nitrite concentration by the Griess reaction. Aerobic exercise (AE) caused a decrease in salivary lipid hydroperoxides in persons with DS (p = 0.001). Aerobic exercise (AE), however, did not affect salivary UA, TAA, and nitrite. This result suggested that AE can be considered as a way to reduce the OS in persons with DS, particularly in the mouth cavity.