Purpose: This study was conducted to evaluate the synergetic effect of using silver diamine fluoride containing potassium iodide and grape seed extract on dentin microhardness. Materials and Methods: Sixty freshly extracted human deciduous second molars were enrolled in this study. Sixty dentin discs were cut from the crown and were randomly divided into four groups according to the applied treatment after dentin demineralization, (15 samples each). In the first group, samples were received no treatment, only stored in artificial saliva (positive control), in the second group, samples were treated with silver diamine fluoride containing potassium iodide only, in the second group, samples were treated with grape seed extract only (GSE), in the third group, samples were treated with silver diamine fluoride containing potassium iodide (SDF), whereas in the fourth group, samples were treated with combined therapy of grape seed extract followed with silver diamine fluoride containing potassium iodide (GSE+SDF). Microhardness measurements were taken for each dentin disc at baseline, after demineralization, and after treatment. Results: There was a statistically significant increase in dentin microhardness after each treatment as compared to the demineralized dentin microhardness. The mean percent change of dentin microhardness was statistically significant increased in GSE, SDF, and GSE+SDF groups when compared to the control group. Conclusions: Considering the limitations of this study, monotherapy of GSE, SDF solution, and their combination can be recommended to enhance the micro-hardness of demineralized dentin. SDF applications after GSE improved the micro-hardness of demineralized dentin when compared to the monotherapy of each treatment.