Purpose: To evaluate the remineralizing potential of cranberry extract and phosphorylated chitosan pretreatment on microhardness and chemical structure of demineralized dentin. Materials and Methods: A total number of 36 dentin samples were divided into four main groups of 9 samples each according to the utilized treatment after demineralization. In the first group, cranberry extract was used, in the second group, phosphorylated chitosan was used. For the third group, combination of cranberry extract and phosphorylated chitosan was used, whereas in the fourth group, no treatment was carried out (control). All groups were subjected to a pH cycling for 3 days. Five microhardness measurements were performed for each dentin sample at baseline, after demineralization, immediately after treatment, after one month and after three months storage in artificial saliva. Two representative samples from each group were selected for SEM/EDAX analysis. Results: Microhardness results revealed significant difference among all treatment groups, cranberry extract + phosphorylated chitosan combination group yielded the highest percentage of change of dentin microhardness, followed by phosphorylated chitosan group, then cranberry extract group. SEM/EDAX confirmed the microhardness results. Conclusions: Phosphorylated chitosan and cranberry extract could be considered as an effective natural treatment options to strengthen demineralized dentin.