This study evaluates the polyphenolic and volatile profile of wines and by-products from Macedonia produced under different vinification procedures. The first goal of this study was the isolation of anthocyanins from grape pomace of three red varieties (Vranec, Merlot and Pinot Noir) by application of countercurrent chromatography. The major anthocyanin was malvidin-3-glucoside and also delphinidin-3-glucoside, cyanidin-3-glucoside, petunidin-3-glucoside, peonidin-3-glucoside and malvidin-3-p-coumaroyl-glucoside were isolated. The “color activity concept” was applied and visual detection thresholds of isolated anthocyanins were determined. The content of trans-resveratrol and its glucoside piceid, resulting antioxidant activity and the relationship between their levels and winemaking technology has been studied in Macedonian red wines from the two main grape varieties Vranec and Merlot. Finally, the liberation of glycosidically bound volatile compounds from white and red wines was performed by using the enzyme mixture “AR 2000” and the obtained volatile profile was compared with that of the wines in which the enzyme “Ednozym Aromatic” during vinification was applied.