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The purpose of this study was to evaluate comparatively the polyphenolic content and the antioxidant activity of selected regional red and white wine varieties, produced in the Republic of North Macedonia. The polyphenolic content was evaluated by measuring the total polyphenol, total flavonoid, total tannin and total anthocyanin contents and the antioxidant activity by applying the DPPH (2,2-diphenyl-1-picrylhydrazyl), FRAP (ferric-reducing antioxidant power) and CUPRAC (cupric ion-reducing antioxidant capacity) assays. Statistical analysis of the results showed that all white wines examined (Smederevka, Temjanika and Zhilavka) belong to the same group, two red wines (Vranec and Kratoshija) belong to another group while the Stanushina red variety shows distinct differences from the other red wines examined.