The kinetics of polyphenol extraction from brewer’s spent grain (BSG), using a batch system, ultrasound assistance, and microwave assistance and the evolution of antioxidant capacity of these extracts over time, were studied. The main parameters of extraction employed in the batch system were evaluated, and, by applying response surface analysis, the following optimal conditions were obtained: Liquid/solid ratio of 30:1 mL/g at 80 °C, using 72% (v/v) ethanol:water as the solvent system. Under these optimized conditions, ultrasound assistance demonstrated the highest extraction rate and equilibrium yield, as well as shortest extraction times, followed by microwave assistance. Among the mathematical models used, Patricelli’s model proved the most suitable for describing the extraction kinetics for each method tested, and is therefore able to predict the response values and estimate the extraction rates and potential maximum yields in each case.