Stevia rebaudiana Betoni (SR) or the candy leaf herbal plant is widely consumed as a non-caloric natural sweetener in substitute of table sugar. The perennial plant is native to South America and is cultivated across the globe. Over the years, there has been an increasing scientific interest in Stevia leaves, which naturally inherent phytochemicals of potent pharmacological properties. Amongst the various pharmacological activities previously evident through in vitro or in vivo studies includes blood sugar regulators, antibacterial, and antiviral properties. Type 2 diabetes mellitus (T2DM), or adult-onset diabetes, is a chronic condition characterized as non-effective insulin production by the pancreas. As a result, blood sugar rises and leads to fatality under an extremely high blood sugar condition. In this study, a library of SR leaf phytochemicals was screened using a comprehensive computational approach for the identification of potential anti-T2DM drug compounds. The in silico inhibitory activities of SR phytochemicals against selected T2DM receptor targets (T2DMrTs) were measured by molecular docking analysis and the best complex, as indicated by the minimum binding affinity and extent of structural interactions, was validated further by molecular dynamics (MD) simulation using the GROMACS webserver. The SR phytochemicals were searched in open-source databases and the corresponding pharmacological properties were predicted by the SwissADME tool. The following proteins were set as the T2DMrTs: α-amylase, α-glucosidase, DPP-4, GLP-1R, PPAR-γ and PTP1B. A total of 177 SR phytochemicals were mined and further screening by molecular docking analysis and pharmacological evaluation identified 19 compounds satisfying the minimum binding energy set at < -7 kcal/mol, Lipinski’s rule of five, and oral bioavailability score. Under all possible receptor-ligand, pair-wise combinations, the complexes showed strong to good stability under a 50 ns MD simulation run. The findings inform new information on SR phytochemicals for T2DM therapeutics and drug development.