Pomegranate is a polyphenol-rich fruit. Studies have shown that extracts prepared from its juice or from different parts of the pomegranate plant have various biological activities including antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, cardioprotective, and antidiabetic. The therapeutic potential has been attributed to various phytochemicals, including ellagic acid, punicic acid, flavonoids, anthocyanidins, anthocyanins, flavonols, and flavones. This review focuses on the scientific evidence of pomegranate juice as hypoglycemic, emphasizing the chemical composition and the possible mechanisms of action associated with this effect. Studies were identified using the PubMed, Scopus, and ISI Web of Science databases to identify relevant articles focused on the hypoglycemic effect of pomegranate juice. The physiological responses to pomegranate juice are reported here, including a decrease of oxidative stress damage, an increase of insulin-dependent glucose uptake, maintenance of β-cell integrity, inhibition of nonenzymatic protein glycation, an increase of insulin sensitivity, modulation of peroxisome proliferator-activated receptor-gamma, inhibition of α-amylase, inhibition of α-glucosidase and dipeptidyl peptidase-4, and decreases in inflammation. Overall, we found a significant hypoglycemic effect of pomegranate in in vitro and in vivo studies and we summarize the potential mechanisms of action.