Glucokinase is, an allosteric enzyme involved in glycolysis, is rapidly regulated in the liver through glucokinase regulatory protein and remains essential for blood glucose homeostasis. The present review provides brief information about the effects of a few selected plants and phytochemicals on human glucokinase activation and gene modulation. A thorough and relevant literature search from several scientific databases, comprising Google Scholar, Web of Science, Scopus and PubMed, was carried out. We highlighted the seven plants (Acorus tatariowii Schott, Allium hirtifolium Boiss, Apache red maize, Mulberry species, Pterocarpus marsupium, Sapium ellepticum, Mangifera indica) and their phytoconstituents ( Tatanans A-C, alliogenin , gitogenin , kaempferol , quercetin and shallomin,1-deoxynojirimycin,cyanidin-3-rutinoside,resveratrol,cyanidin-3-glucoside,oxyresveratrol, lupeol, alpha-tocopherol, uteolin-7-glucoside, amentoflavone, and Mangiferin) on human glucokinase enzyme activation and gene modulation. This review concluded that investigation of glucokinase activators of plant origin is the major research focus in the management of type 2 diabetes.