Objectives: This study investigates the potential application of Roselle Extracts (Hibiscus sabdariffa L.) in managing diabetes mellitus. The previous study shown the impact of Roselle Extracts on blood glucose levels and insulin sensitivity in diabetic, as well as the identification of compounds found in Roselle Calyces as potential Phosphoenolpyruvate carboxykinase (PEPCK) inhibitors for treating type 2 diabetes mellitus. Methods: In first we search about the effects of Roselle Extracts on blood glucose levels, insulin sensitivity, pancreatic alpha-amylase and intestinal alpha-glucosidase enzymes inhibition, pancreatic lipase activity, and gene expression related to gluconeogenesis, glycolysis, and lipogenesis in debate. Then we analyzes the physicochemical properties and pharmacokinetics of potential PEPCK inhibitors present in Roselle Calyces using the SwissADME web tool. Results: Metformin has high solubility in aqueous liquids and is easily absorbed during digestion. It does not inhibit most cytochrome P450 liver enzymes and cannot cross the blood-brain barrier, making it pharmacokinetically acceptable. Hibiscetin, Gossypetin, and Flavylium are also soluble in aqueous liquids, but their weak digestive absorption limits their effects on blood. However, their effect on secretory enzymes in the digestive tract is well known. On the other hand, 3,4-dihydroxybenzoic acid has higher digestive absorption and greater availability in the blood, making it a potential antidiabetic compound. Beta-Sitosterol has the highest skin absorption among the studied compounds, while Flavylium compounds show poor skin permeability. Both Metformin and Beta-Sitosterol do not inhibit cytochrome P450 liver enzymes, which is beneficial for their pharmacological profiles. These findings offer valuable insights into the potential uses and limitations of these compounds in various therapeutic applications. Conclusions: The previous findings suggest that Roselle Extracts and its identified compounds could play a significant role in managing diabetes mellitus. The Physicochemical Properties and pharmacokinetic properties of these compounds can guide the development of new drugs and formulations, ultimately improving patient outcomes and overall healthcare.