Purpose: To evaluate the effect of Miswak and Grape seed extract (GSE) on enamel and dentine subjected to artificial acid challenge in-vitro. Materials and Methods: A total of thirty sound freshly extracted sound human permanent periodontally affected upper molars were used. 30 enamel specimens were cut from the buccal surface of the teeth and 30 dentin specimens were cut from the cervical root area. All specimens were polished to obtain a flat polished surface. Ethanolic miswak extract was prepared by percolation method. Solutions of 10% ethanolic miswak extract, 6.5% Grape seed extract and 0.05% sodium fluoride were prepared. Specimens were divided into two groups (n=30); enamel and dentin. Each group was further divided into three sub-groups (n=10) according to the material used. Group1; treated with 10% ethanolic miswak extract solution. Group2; treated with 6.5% GSE solution. Group3; treated with 0.05% sodium fluoride solution (positive control). Specimens were individually subjected to alternative treatment/pH cycling regimen for 7 days. Radiodensity (change in mineral content) for each enamel and dentine specimen was assessed before and after pH cycling using digital radiography. Data were statistically analyzed; the significance level was set at p ≤0.05. Results: Miswak and GSE showed a high percent gain in enamel and dentine radiodensity compared to fluoride. Conclusion: Miswak and GSE are beneficial to both enamel and dentin through increasing their resistance to acid attacks.