Murrayae exotica is a traditional Chinese medicine widely grown in southeast China. A Box–Behnken design of response surface methodology was employed to further optimise ultrasonic-assisted extraction conditions for M. exotica leaves total flavonoids (MELTF). The results showed that the optimised extraction conditions were an ultrasonic power of 240 W, an ultrasonic temperature of 60 °C, a solvent concentration of 76%, an ultrasonic time of 55 min and a liquid–solid ratio of 22 mL · g ⁻¹ . Under these conditions, 8.59 ± 0.34 mg · g ⁻¹ was achieved as the mean experimental value of extraction yield, which amounts to 2.56 times that of ethanol leaching extraction. As compared to MELTF, MELTF after purification (MELPTF) had a higher purity of 9.96%, which was nearly nine times higher than that of MELTF (1.26%). As compared to MELTF, MELPTF had higher α-glucosidase and α-amylase inhibitory activities as well as DPPH ^· and ABTS ^·+ scavenging activities with IC ₅₀ values of 0.021, 0.094, 0.245 and 0.113 mg · mL ⁻¹ , which are 1.33, 2.12, 3.17 and 1.78 times higher than those of MELTF (0.028, 0.199, 0.777 and 0.201 mg · mL ⁻¹ ). The study thus demonstrates the eligibility of MELPTF to be considered as a multifunctional bioactive ingredient having potential applications in anti-hyperglycaemic pharmaceutical formulation and as an antioxidant in functional foods.