Ice plant (Mesembryanthemum crystallinum) extract (IPE) is a rich source of d-pinitol, which is widely known to have potential anti-diabetic effects. In the present study, response surface methodology (RSM) was used to optimize d-pinitol extraction conditions with the Box-Behnken design. We then evaluated the anti-diabetic effects properties of IPE that was extracted under optimized conditions (53 °C, 119 min extraction time, and 1 : 11 dilution) in type 2 diabetic Goto-Kakizaki (GK) rats. IPE (400 mg kg-1 day-1) effectively controlled the increased fasting blood glucose level (decreased by 45% vs. GK-control rats) and impaired glucose tolerance (decreased area under curve (AUC) of glucose values by 24%, p < 0.05 vs. GK-control rats) after eight weeks of treatment. Furthermore, IPE significantly improved pancreatic islet morphology, β-cell survival, and insulin secretion in diabetic rats, thus contributing to the antihyperglycemic effect. Finally, prebiotic effects of IPE on gut microbiota were observed and included increased abundance of the beneficial bacteria Bacteroidales_S24-7 and Ruminococcaceae_UCG-014 and decreased abundance of Treponema_2 and Lactobacillus. Overall, IPE has a substantial effect on attenuating hyperglycemia and modulating gut microbiota composition in diabetic GK rats. Therefore, IPE might be a promising functional food for the prevention of diabetes.