MDPI Background/Objectives: The extraction and encapsulation of Tanacetum parthenium L. (feverfew) represent highly relevant approaches for maximizing the recovery and protection of its bioactive phytocomplexes, particularly the main active compound, parthenolide (PAR). The present study aimed to develop and optimize a cyclodextrin-based extraction and encapsulation method for T. parthenium to improve the chemical and physicochemical properties and biological activity of bioactive-rich phytocomplexes. Methods: The extraction process was optimized by comparing conventional maceration (ME) and ultrasound-assisted extraction (UE), using different ethanol–water mixtures as extractants, with and without hydroxypropyl-β-cyclodextrin (CD) as an extraction enhancer. The highest PAR yield (approximately 6.3 mg/g dried biomass), combined with enhanced total polyphenol and flavonoid contents, was achieved using 50% (v/v) ethanol with 0.5% CD under UE. The optimized extract was spray-dried to produce powder formulations, with or without carrier material, which have been characterized for their technological, chemical, physicochemical, structural, and biological properties. Results: The inclusion of CD significantly improved process yield (approximately 65% compared to 47% for the non-encapsulated extract) and reduced residual moisture content, indicating enhanced drying efficiency and improved powder stability. Furthermore, the encapsulated formulation demonstrated preserved antioxidant and anti-inflammatory activity in cell-based assays. Conclusions: The developed CD-based encapsulation method represents a promising strategy for stabilizing feverfew bioactives and enhancing their potential applicability in pharmaceutical and dermo-cosmetic formulations. Cyclodextrin-Assisted Extraction and Encapsulation of Parthenolide- and Polyphenol-Rich Feverfew (Tanacetum parthenium L.) for Enhanced Bioactivity info:eu-repo/semantics/article http://creativecommons.org/licenses/by/4.0/legalcode first_pagesettingsOrder Article Reprints Open AccessArticle Cyclodextrin-Assisted Extraction and Encapsulation of Parthenolide- and Polyphenol-Rich Feverfew (Tanacetum parthenium L.) for Enhanced Bioactivity volume: 19 number: 8 startpage: 1176 application/pdf 9224820 bytes Ćujić Nikolić, Nada Lazarević, Dajana Jovanović, Aleksandra A. Jovanović, Jelena Šavikin, Katarina Nizar, Nibina Ilić, Gorana Vladisavljević, Goran Trtić-Petrović, Tatjana https://phaidrabg.bg.ac.rs/o:39459 doi:https://doi.org/10.3390/ph19081176 2026 eng feverfew (Tanacetum parthenium L.); cyclodextrin; extraction; encapsulation; spray drying; antioxidant; anti-inflammatory