Background: Some studies have shown that casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and acidulated phosphate fluoride (APF) gel can protect teeth against erosion. The aim of this study was to assess whether CPP-ACP and fluoride could reduce enamel wear rates under erosive conditions simulating abrasion and acidic diet regimen. Materials and Methods: Enamel specimens consisted of 3 experimental groups (receiving CPP-ACP, APF or both) and a control group. Specimens were subjected to 5,000 wear cycles at a load of 30 N and a pH of 3 in a tooth wear machine. The amount of wear was determined by stereomicroscope. Data were analyzed using one-way analysis of variance and Tukey post hoc tests (α = 0.05). Results: Mean wear rate (mean±SD) was 194.6±49.2 micrometers in CPP-ACP group, 197.6±39.5 in APF group, 134.6±44.7 in combination group and 266.2± 22.7 in the control group. Statistical analysis indicated significantly higher wear rate in the control group than the experimental groups and also in the CPP-ACP and APF group than the combination group (P<0.05). Conclusions: We concluded that although either CPP-ACP or APF can protect enamel against wear, their combination provides significant enamel wear reduction. These findings would lead to new strategies for the clinical management of tooth wear.