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BACKGROUND In this study, the optimal conditions for the extraction and purification of glycyrrhizic acid from Radix Glycyrrhizae (RG) and baicalein and wogonin from Radix Scutellariae (RS) by foam fractionation were studied on the basis of central composite design (CCD) and response surface methodology. RESULTS The results showed that herbal proportion (RG: RS), gas flow and ethanol concentration were the main factors guiding the foam fractionation of RG and RS. The optimum technological parameters were obtained as follows: herbal proportion (RG:RS), 1.86:1.14; gas flow, 109 mL min-1 ; and ethanol concentration, 53%. Under the optimal operating conditions, the maximal extraction yields of baicalein, glycyrrhizic acid and wogonin were 56.67 mg g-1 , 13.25 mg g-1 and 9.51 mg g-1 , respectively, which were 2.32-fold, 1.22-fold and 1.84-fold higher than those of ultrasonic extraction and 17.28-fold, 1.15-fold and 9.91-fold higher than those of ultrasonic extraction without hydrolysis, respectively. Investigations on the antioxidant activity showed that the foam fractionated extract exhibited better free radical scavenging activity (IC50 13.80 μg mL-1 ) than that of the ultrasonic extract (IC50 223.00 μg mL-1 ). The antibacterial activity showed that the minimum inhibitory concentrations of the foam fractionated extract against Staphylococcus aureus (S. aureus), Candida albicans (C. albicans), Group A Streptococcus (Group A S.) and Pseudomonas aeruginosa (P. aeruginosa) were 1.38 mg mL-1 , 1.38 mg mL-1 , 0.69 mg mL-1 and 5.50 mg mL-1 , respectively. CONCLUSION The results indicate that the foam fractionated extract exhibited better extraction yields and free radical scavenging activity than that of the ultrasonic extract. Therefore, this fast and eco-friendly method was established and could be a basis for the extraction and separation of other active constituents from herbal medicines. This article is protected by copyright. All rights reserved.