Abstract This study evaluated the effect of Euclea natalensis gel on the reduction of erosive wear with or without abrasion, in enamel and dentin. During two five-day experimental crossover phases, volunteers (n = 10) wore palatal devices containing human enamel and dentin blocks (E = 8 and D = 8). The gel was applied in a thin layer in the experimental group, and was not applied in the control group. In the intraoral phase, volunteers used the palatal appliance for 12 h before the gel treatment, and were instructed to start the erosive challenges 6 h after the gel application. Erosion was performed with Coca-Cola® (for 5 min) 4 times/day. The appliance was then put back into the mouth and was brushed after 30 minutes. After intraoral exposure, the appliances were removed and the specimens were analyzed using profilometry (mean ± SD, μm). The Euclea natalensis gel caused less wear in enamel in the experimental group (EROS = 12.86 ± 1.75 µm; EROS + ABRAS = 12.13 ± 2.12 µm) than in the control group (EROS = 14.12 ± 7.66 µm; EROS + ABRAS = 16.29 ± 10.72 µm); however, the groups did not differ from each other significantly. A statistically significant value was found for erosion and eros + abrasion in dentin (p = 0.001). Euclea natalensis may play a role in the prevention of dentin loss under mild erosive and abrasive conditions. A clinical trial is required to confirm these promising results in a clinical situation.