In the current study, bioactive compounds of Vitis vinifera (Perlette) were extracted using an ultrasound-assisted extraction technique. The central composite design of response surface methodology (RSM) was used to determine the effect of time, temperature, and concentration of acetic acid on response variables that include extract yield, total phenolic content (TPC), total flavonoid content (TFC), and antioxidant activity of Vitis vinifera extracts. The results of the central composite design of RSM revealed that the quadratic polynomial model is best fitted to experimental results, with all the responses having a regression coefficient greater than 0.9. Optimized extraction levels include 26.5 min, an extraction temperature of 59 °C, and an acetic acid concentration of 62.9% with good extraction yield results of 34.95 g/100 g dry weight (DW) of grapes, TPC 34.38 mg gallic acid equivalent per gram (GAE/g) DW, flavonoid content 10.21 mg quercetin equivalents per gram (QEQ/g) DW, and antioxidant activity of 9.11 mg/100 mL ascorbic acid equivalent. The present study showed that acetic acid can be effectively used for the ultrasound-assisted extraction of polyphenols, flavonoids, and antioxidants of Vitis vinifera. These optimized conditions can be used for the extraction of bioactive compounds that can be for the development of nutraceutical products.