Since biotransformation processes generally affect the biological activities of phytochemical compounds, bioavailability is one of the primary steps in determining the potency of the activity. Previous studies have shown that in vitro antioxidant capacity of phytochemicals cannot completely reflect real health benefits. Clematis species (Ranunculaceae) are used to eliminate the symptoms of many diseases including particularly in the treatment of rheumatic diseases in Turkey, however the number of studies conducted is limited. In the light of this information, the total phytochemical profile of the extract of aerial parts of C. viticella prepared with 80% methanol and the gastrointestinal digestion products and the antioxidant activity profile were evaluated by subjecting them to the in vitro simulation model of the human digestive tract in the study. It was observed that both total phytochemical content and antioxidant activity decreased after simulated human digestion. Moreover, this study was shown potential bioaccessibility and bioavailability of total phenol, phenolic acid, flavonoid, and saponin content found in the aerial parts of Clematis viticella were reduced. Consequently, these indicate that it can result from the complicated interaction of compounds in the plant matrix in an in vitro simulated human digestion.