Sideritis scardica and Sideritis syriaca are considered highly valuable plant materials and their total polyphenols (TP) and total flavonoids (TF) extracts can be employed in nutraceutics and cosmetics. A two-step process was proposed consisting in the ultrasound-assisted extraction (UAE) and concentration of the biologically active compounds via nanofiltration (NF). An extensive comparison between UAE and conventional high-temperature stirring was performed, taking into account the effect of process parameters such as solvent, temperature and ultrasonication. In terms of radical scavenging activity and time optimization, UAE was found more effective, providing - after only 1 h - extraction yields comparable to 20 h of the conventional thermo-mechanical method. The extract was then concentrated by nanofiltration in tangential mode at 20 bar using 300 and 500 Da cut-off Duramem membranes. Permeate and rejection flux was monitored during the filtration process. The lower molecular weight membrane showed higher permeability towards TP and TF and contributed to a more stable flux and lower fouling processes. To predict operational drawbacks, computational fluid dynamic simulations were performed to model the complex rotational flow occurring during membrane filtration. (C) 2019 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.