•Studies have been focused on mulberry fruits and their bioactive substances.•Mulberry’s polyphenols profile has been fractionalized, conversely with their bioaccessibility.•Mulberry’s health benefits have been well acknowledged especially antioxidant activity.•The processing steps should be optimized to keep the stability of mulberry’s polyphenols. Mulberry (Morus sp.) fruits provide high levels of anthocyanins, quercetin glycoside, and chlorogenic acid. Recently, mulberry’s polyphenols and their functionalities are spotlighted in different ex vivo and in vivo studies. Meanwhile, the deficiency of systematic knowledge on the health effects and polyphenols composition greatly hinders the development of mulberry as a sustainable fruit. This review briefly summarises the polyphenol compositions, metabolism, health benefits, and their stability in different mulberry production steps. These claimed health effects include anti-oxidative, anti-cancer, anti-diabetes, anti-obesity, and other related effects. However, although the current evidence is promising, further clinical studies are needed to evaluate the role of mulberries' polyphenols to support human health. Besides, the mechanisms by which they confer the health benefits, the bioavailability studies on mulberry’s polyphenols are also scarce. We compile the research findings from the available literatures within the last two decades, and we also suggest some future perspectives in this review.