Grapes are a rich source of biomolecules, such as phenolic acids, flavonoids and anthocyanins. The aim of the present study was to investigate the chemical composition by optimized extraction method and the in vitro biological activities of polyphenolic extracts obtained from skin and seed of Mascara region cinsault grape (Vitis vinifera L.). The optimized extraction was based on different ratio and polarity of solvents (acetone, methanol, ethanol and water), pH and temperature, to separate the individual polyphenolic compounds. The determination of the qualitatively and quantitatively of polyphenolic extracts was performed using Folin–Ciocalteu, ALCl3, vanillin and high performance liquid chromatography (HPLC). In addition, the antioxidant and in vitro antimicrobial activities were evaluated against representative resistant human pathogens. Significant variations between different extraction solvent were duly noted. The methanolic aqueous extract (70%) exhibited high total polyphenols (TPC) (290±7.21 mgEAG/100g) for seed and high total flavonoids level (TFL) (194,5±5,87 mgEQ/100g) for skin. The results obataines by HPLC analysis of the extract with the best extraction performance allowing us to identify fourteen (14) compounds. Concerning the evaluation of antioxidant properties of extracts using various assays such as ABTS DPPH and FRAP methods, the results obtained were high (0.178mg/ml for IC50). All extracts of skin and seed have shown very significant inhibitory activity against pneumoneae. Despite these significant results, some germs have shown remarkable resistance in the presence of some polyphenolic extracts