Polyphenols are organic compounds that can be found in food, especially in fruits, vegetables, and their products. It was shown that their presence significantly affects the properties of food products and that the consumption of food rich in phenolic compounds has a beneficial effect on human health. The subjects of this research were polyphenols: anthocyanins, flavonols, and flavan-3-ols in the skin of grapevine variety Regent. Polyphenols from grape skins were extracted via microwave-assisted extraction (MAE) and matrix solid-phase dispersion (MSPD) as unconventional and green techniques. Therefore, the main aim of this work was to optimize the conditions for the extraction of polyphenolic compounds from grape skin using MAE and MSPD. The extracts were analyzed using high-performance liquid chromatography with a diode array detector and fluorescence detector. Analyses showed that MAE was a very effective method for extracting polyphenolic compounds from grape skin with 10 mL of 60% ethanol for 5 min at 40 °C. The best results for the MSPD extraction of polyphenolic compounds from grape skin were obtained with phenyl as an MSPD sorbent with 10 mL of acetonitrile:water 50:50 v/v as an elution solvent. This scientific research can be used for the better use of grapes as a basis for obtaining flavonoids for commercial purposes.