Type 2 diabetes mellitus is a metabolic disease categorized by hyperglycemia, resistance to insulin, and ß-cell dysfunction. Around the globe, approximately 422 million people have diabetes, out of which 1.5million die annually. In spite of innovative advancements in the treatment of diabetes, no biological drug has been known to successfully cure and avert its progression. Thereupon, natural drugs derived from plants are emerging as a novel therapeutic strategy to combat diseases like diabetes. The current study aims to investigate the antidiabetic potential of natural compounds of Oryza sativa L. indica (black rice) in disease treatment. Antioxidant activity and alpha amylase assays were performed to evaluate the therapeutic potential of the extract of Oryza sativa L. indica. Gas chromatography-mass spectrometry (GC-MS) was used for identification of constituents from the ethanol extract. ADMET profiling (absorption, distribution, metabolism, excretion, and toxicity), network pharmacology, and molecular dynamics simulation were employed in order to uncover the active ingredients and their therapeutic targets in O. sativa L. indica against type 2 diabetes mellitus. GC-MS of the plant extract provided a list of 184 compounds. Lipinski filter and toxicity parameters screened out 18 compounds. The topological parameters of the protein-protein interaction (PPI) were used to shortlist the nine key proteins (STAT3, HSP90AA1, AKT1, SRC, ESR1, MAPK1, NFKB1, EP300, and CREBBP) in the type 2 diabetes mellitus pathways. Later, molecular docking analysis and simulations showed that C14 (1H-purine-8-propanoic acid, .alpha.-amino-2, 3, 6, 7-tetrahydro-1,3,7-trimethyl-2,6-dioxo-) and C18 (cyclohexane-carboxamide, N-furfuryl) bind with AKT1 and ESR1 with a binding energy of 8.1, 6.9, 7.3, and 7.2kcal/mol, respectively. RMSD (root-mean-square deviation) and RMSF (root-mean-square fluctuation) values for AKT1 and ESR1 have shown very little fluctuation, indicating that proteins were stabilized after ligand docking. This study suggests therapeutic drug candidates against AKT1 and ESR1 to treat type 2 diabetes mellitus. However, further wet-lab analysis is required to discover the best remedy for type 2 diabetes mellitus.