This work studied the effects of ultrasound-assisted liquid-state fermentation on the content of peptides and bioactivity of fermented soybean meal (FSBM) with Bacillus subtilis. Based on the optimization of basic ultrasonic parameters, effects of the main parameters including power density, incubation temperature and ultrasonic time on in vitro ACE inhibitory activity, peptides content and biomass of B. subtilis were investigated via Box-Behnken experimental design. Three mathematical models were determined to show the effects of each variable and their combinatorial interactions on dependent variables. A set of preferred condition was determined to be at power density of 0.08 W/mL for 1 h with an initial incubation temperature of 36.7 degrees C, according to the desirability function analyses. Under these conditions, the experimental values of in vitro ACE inhibitory activity, peptides content and biomass increased by 26.4%, 36.2% and 55.0% compared to those of the control, respectively, accompanied by the improvement of the peptides yield, purity and conversion rate in varying degrees. Additionally, FSBM resulted in a significant decrease of systolic blood pressure by 20.7 +/- 1.8 mmHg in spontaneously hypertensive rats at 3 h. These results suggest that ultrasonication is an efficient solution for enhancing fermentation to produce bioactive components from agroindustrial by-products.