In this study, the response surface methodology was used to optimize the ultrasonic extraction of polysaccharides from Radix pueraria lobata. The first parameter of interest was ultrasonic extraction to investigate its effect on the polysaccharide content within Radix pueraria lobata. Based on single-factor experiments analysis, the independent variables including time, solid–liquid, and times were used for further optimization of the extraction of RPL polysaccharides by Box-Behnken design (BBD). Optimal conditions showed that the maximum polysaccharide content was 1.235 mg/g. The molecular weight (Mw), Fourier transformation infrared (FT-IR) spectroscopy, and proton nuclear magnetic resonance (HNMR) spectroscopy were used for structural characterization in this study. The scavenging activities of Radix Pueraria lobata against DPPH, ABTS, and OH were remarkable, and they were concentration dependent.