The aim of this investigation was to assess the potential of Phlomis aurea extracts [hexane (Hex), ethyl acetate (EtOAc) and methanol (MeOH)] on anti-diabetic property using in vitro yeast cell model and inhibited α-amylase, α-glucosidase and sucrase activity. Our study focused on the chemical constituents of the most active extract of P. aurea plant as anti-diabetic activity and molecular docking investigation of the ligand (bioactive compounds) in the dynamic restricting site of target protein (α–glucosidase, α-amylase, and sucrase). EtOAc extract exhibited the most effective extract where, It significantly increased yeast cells capacity to absorb glucose (86.24%) and inhibited α-amylase, α-glucosidase and sucrase activity with IC50 values (1.99, 1.22 & 2.1 mg/mL) as compared to the IC50 value (2.51, 1.67 & 0.89 mg/mL), of acarbose reference drug, respectively. EtOAc extract containing a large amount of phenolic and flavonoid compounds, as more than 68 phenolic compounds were identified using LC-MS technique, where chalcone, diosmin, naringenin, rhoifolin, apigenin-7-O-glucoside, chlorogenic acid, luteolin-7-O-glucoside, hesperidin, quinic acid, peonidine-3-O-glucoside chloride, apigenin, acacetin, 7-hydroxy-4-methylcoumarin, cyanidin-3-glucoside, datiscin, were the high concentration of identified phenolic constituents. The majority of these compounds exhibited strong binding affinities to α -amylase, α-glucosidase and sucrase catalysts and showed great in-silico brings about correlation with reference inhibitor against target compounds.