The prevalence of diabetes mellitus continues to rise on a global basis, making this entity one of the most pressing issues facing public health nowadays. Generally, diabetes mellitus is characterized by increased blood sugar levels caused by insulin secretion or action abnormalities. Natural products have become more popular in treating various types of diseases, including diabetes mellitus, due to their minimal adverse effects. Promoting the peroxisome proliferator-activated receptor γ (PPARG) activation is an anti-diabetic strategy due to its biological function for adipocyte storage, mobilization, differentiation, and insulin sensitivity. This study aims to evaluate diosgenin and multiflorenol in silico as anti-diabetic drug candidates by targeting PPARG. Several analyses, such as molecular docking, protein target prediction, biological function prediction, protein-protein interaction, and pharmacokinetics analyses were carried out in this study. Computational prediction showed PPARG have involved in several activities, such as fat cell differentiation, fatty acid oxidation, fatty acid transport, and cellular response to fatty acid. The binding affinity score revealed that diosgenin and multiflorenol have a higher value than the control drug. Other characteristics, such as chemical interaction, amino acid residues, and physicochemical properties, demonstrated supportive drug development outcomes. Therefore, based on our findings, we suggested that diosgenin and multiflorenol, both of which target PPARG, would hold promise as potential candidates for an anti-diabetic drug.