Although there is a wide array of antioxidant studies and related phenolic antioxidants on plants, bioavailability phenomenon is often neglected. Design of this study based on evaluation of difference in antioxidant potential and phenolic profile of V. opulus fruits before and after in vitro gastrointestinal human digestion. For this purpose two extracts (methanolic and aqueous) were prepared from its fruits. After the digestion simulation procedure, total phenolic, phenolic acid, flavonoid contents were determined for all phases of digestion. High performance thin layer chromatography (HPTLC) was used for measurement of chlorogenic acid, major bioactive component of the extracts. Bioavailability index was calculated for all phenolic content assays and for the bioactive compound for accurate determination of alterations in phenolic profile via in vitro human digestion. For revelation of the precise antioxidant potential of fruit extracts, a couple of free radical scavenging (DPPH and DMPD) and metal reducing potential (CUPRAC and FRAP) assays and in addition a total antioxidant capacity assay were conducted on all phases. The results showed that the methanolic extract is superior to aqueous counterpart in terms of phenolic profile and antioxidant properties. Also, the major metabolite was negatively influenced by in vitro simulation of human digestion.