The ability of individual and combined extracts of ginger and persimmon to target BCSCs subpopulation and restore the expression of tumor suppressive miRNAs, miR-200c, miR-30a and miR-128, is evaluated in this study. Combined treatment led to decreasing CD44⁺ CD24^- subpopulation in MDA-MB-231 to a percent lower than both individual extracts, however, the combined treatment didn't affect the expression of pluripotency-associated genes, OCT3/4, SOX2 and NANOG, which are down-regulated as a consequence of both individual extracts treatment. Bioinformatics predicted DNMT3A as the target of miR-200C and miR-30a, and ABCB9 as the target of miR-128a. Both individual extracts exerted an activating effect on miRNAs (except persimmon extract on miR-30a) and an inhibitory effect on their targets DNMT3a and ABCB9 expression. Additionally, combined treatment keeps the activating effect of individual extracts on miRNAs, decrease the inhibitory effect of individual extracts on ABCB9, and reversed it into activating effect in the case of DNMT3a. Moreover, we found a significant decrease in miR-200c promoter methylation after individual treatments, which could represent a positive feedback loop between miR-200c and its target DNMT3a, however, this effect on methylation status is absent in the case of combined treatment. The methylation of LINE1, the index of global DNA methylation, was increased in response to ginger extract treatment, predicting increasing in genomic stability. Our finding highlighted the role of individual and combined aqueous ginger extract and methanolic persimmon extract to subdue BCSCs by modulating the expression of tumor-suppressive miRNAs, despite the variation of molecular genetics and epigenetic response of candidate genes