In order to improve the extraction rate of flavonoids from Hibiseu manihot L flower and explore its application in cosmetics, Hibiseu manihot L flower was used as raw material, ultrasonic-assisted extraction was used to extract flavonoids from Hibiseu manihot L flower. The extraction process was optimized by a single factor experiment and an orthogonal experiment, and the antioxidant activity and safety of flavonoids extracted from Hibiseu manihot L flower under the optimal process conditions were evaluated. The results showed that the optimum extraction process of flavonoids from Hibiseu manihot L flower was as follows: ultrasonic power 300 W, ethanol volume fraction 80%, ultrasonic time 35 min, extraction temperature 75 °C, solid-liquid ratio (g ∶ mL) 1:15. The maximum extraction rate of flavonoids from Hibiseu manihot L flower was 89.97%. 1 g/L flavonoids from Hibiseu manihot L flower had the highest scavenging rates of DPPH free radical and hydroxyl radical, which were 94.81% and 95.24%, respectively. The half maximal inhibitory concentration (IC50) values were 0.1060 and 0.07006 g/L, respectively. The flavonoids from Hibiseu manihot L flower with a mass fraction of 3.13% had the largest radical scavenging rate (85.61% ) on ABTS cation-free radical. When the concentration of flavonoids from Hibiseu manihot L flower was less than 0.4 mg/mL, the hemolysis rate of red blood cells was less than 10%, which belonged to the mild stimulation rating. Flavonoids from the Hibiseu manihot L flower at a concentration of 1 mg/mL had no hemolysis on the chick embryo chorioallantoic membrane.