Over many centuries, spices have been and are globally utilized in foods and drinks, as well as in pharmaceuticals industries. Spices are rich in health-beneficial chemical constituents that include diet- derived polyphenols, terpenes, polysaccharides, lipids, organic acids, and raw fibres. Stem cells can self- renew and differentiate into major cell types. However, malignant stem cells can invade and kill nearby tissue as well as spread to other body parts through the blood and lymph systems leading to several diseases including cancers affecting the lungs, liver, breasts, pancreas, stomach, colorectum, and cervix. The purpose of this mini-review is to highlight the contributions of recent research on the role of different diet-derived polyphenols from spices mainly cardamom (Elettaria cardamomum); cinnamon (Cinnamomumzeylanicum); clove (Syzygiumaromaticum); ginger (Zingiberofficinale); nutmeg (Myristicafragrans); pepper (Pipernigrum); saffron (Crocussativus); turmeric (Curcumalonga) and vanilla (Vanilla planifolia) in the modulation of the self-renewal of normal and malignant stem cells. Recent researches have demonstrated that predominant compounds; curcumin, crocetin, crocin, gingerols, shogaols, myristicin, piperine, and vanillin possess immunomodulatory effects that specifically inhibit or suppress the proliferation of cancer cells by stimulating the development of normal stem cells, encouraging apoptosis, and activating the expression of protective genes that prevent the formation of malignant cells. More attention should focus on spices and their advanced applications into nutraceuticals for the prevention and management of chronic illnesses. Further work using a combination of in vitro and in vivo methods is needed to fully understand the synergistic impacts of combining more of these compounds to express their modulation effect on the self-renewal of stem cells.