To optimize the extraction process and activity detection of total flavonoids from Ficus Pumila. A Box–Behnken design of response surface methodology was employed to further optimize ultrasonic-assisted extraction (UAE) conditions for Ficus Pumila stems total flavonoids ( FPSTF). The results showed that optimized extraction conditions were ultrasonic power of 240 W, solvent concentration of 61%, ultrasonic time of 61 min and liquid-solid ratio of 25 mL/g. Under these conditions, the mean experimental value of extraction yield (1.07%) was achieved, which was about 2.14 times that of ethanol leaching extraction. As compared to FPSTF, FPSTF after purification ( FPSPTF) had higher purity of 11.09%, which was nearly 4.37 times higher than that of FPSTF (2.54%). As compared to FPSTF, FPSPTF had higher α-glucosidase and α-amylase inhibitory activities as well as DPPH· and ABTS·⁺ scavenging activities with an IC ₅₀ value of 0.005, 0.008, 0.22 and 0.08 mg/mL, which was 6.00, 16.50, 1.68 and 2.50 times higher than that of FPSTF (0.030, 0.132, 0.37 and 0.20 mg/mL). FPSPTF from F. Pumila could be considered as multifunctional bioactive ingredients to be used in anti-hyperglycemic pharmaceutical formulation and antioxidant.