© 2020 SAABThe genus Salvia is regarded as an important medicinal plant and also as spice worldwide. Current report might be counted as one of the first investigations to reveal the enzyme inhibitory and antiglycation activities, together with phenolic and antioxidant profiles of 80% methanolic extract prepared from the aerial parts of S.virgata (SVM). Furthermore, the bioavailability parameters of major phenolic compounds in SVM were evaluated. An in vitro human digestion simulation model composed of both gastric and intestinal phases was used for this purpose. Total phenolic, phenolic acid and flavonoid components of each of these phases were calculated in order to assess the phenolic profile of the samples. In addition, quantitative analysis of major bioactive compounds (rutin and rosmarinic acid), before and after the simulation, was practiced by employing High Performance Thin Layer Chromatography (HPTLC) system. Moreover, the potential of non-digested (ND) and bioavailable (IN) phases on the inhibition of diabetes-related enzymes (α-amylase and α-glucosidase) was determined. Also, the inhibitory effect of the samples on the advanced glycation end products (AGEs), formed due to hyperglycemia, was detected. In addition, cholinesterase enzyme inhibition activity of both ND and IN samples was determined. Since, the role of oxidative stress on diabetes and neurodegenerative diseases is well-known, the antioxidant potential of the samples was also estimated by different methods: DPPH and DMPD tests for free radical scavenging activity, FRAP and CUPRAC tests for metal reducing activity and total antioxidant capacity test, as well. The results showed that total phenolic contents, antioxidant potential and diabetes-related and cholinesterase enzymes inhibition of the bioavailable phase were lower than non-digested sample. Besides, in vitro human digestion simulation system had a declining influence on the concentrations of the major bioactive metabolites (rutin and rosmarinic acid).