The quality of grape cultivars not only depends on the grape cultrvar but also is influenced by the molecular concepts and agro-climatic factors. For this purpose, four different grape cultivars were collected from five different locations in Siirt province (Turkey). Totally twenty different grape cultivars were investigated. In the present study, the antioxidant activity (total phenolic, flavonoid, proanthocyanidin content, DPPH and FRAP activity) in seeds were indicated and phylogenetic analysis (cpDNA;trnL-F region) of twenty native grape cultivars were imestigated to construct their phylogenetic tree. According to reported data on antioxidant activity and content of phytochemicals, all cultivars exhibited different values from each other, but Rutik and Gad?v cultivars were found as significantly higher in comparison to others According to bioinformatics analysis, twenty grape cultivars were distributed into six different major groups. Rutik and Sevkeye cultivars exhibit significant distinction from other grape cultivars. The phylogenetic analysis was also associated and supported with the results of obtained data from bioactivity. The bioactivity and phylogenetic analysis were firstly identified and quantified in these grape cultivars, however, with regard to obtained data from the current study, the grape cultivars grown in Siirt province were indicated significant and valuable results and as a result, these cultivars have to be evaluated before extinction.