The aim of this study was to evaluate the effect of silver diamine fluoride and grape seed extract on the microstructure and mechanical properties of carious dentin following exposure to acidic challenge. Ninety-eight molars with occlusal caries were used. In the control group the specimens were kept in distilled water. In the GSE group, the specimens were immersed in 6.5% grape seed extract solution for 30 minutes. In the SDF group, the specimens were immersed in 30% SDF solution for 4 minutes. In the GSE+SDF group, the specimens were immersed in 6.5% grape seed extract solution for 30 minutes and then exposed to 30% SDF solution for 4 minutes. All the groups underwent pH cycling model for 8 days. Microhardness measurements were taken at the baseline before surface treatments and after pH cycling. Elastic modulus was measured, after pH cycling. In the control group, the final hardness was significantly lower than the initial hardness (P = 0.001). In the SDF group, the final hardness was significantly higher than the initial hardness (P < 0.001). There was no significant difference between the initial and final hardness values in the GSE and GSE + SDF groups (p = 0.92, p = 0.07). The H1-H0 in the SDF group was significantly higher than the other groups (P<0.05). Moreover, elastic modulus of the experimental groups except GSE+SDF group was significantly higher than control. The highest mean elastic modulus was detected in the SDF group (P<0.001). The use of SDF and GSE prior to the acid challenge improved mechanical properties. Microstructural investigation, using scanning electron microscope showed dentin structure protection against acid challenges with SDF treatment and collagen matrix stabilization with GSE treatment. However combined use of these agents was not beneficious.