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Essential oils were hydrodistilled from Tunisian plant material and chemically characterized via GC\u2010MS, revealing carvacrol, 1,8\u2010cineole, and D\u2010limonene as the dominant compounds, respectively. The antidiabetic (\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010amylase inhibition) and antioxidant activities of individual oils and their mixtures were evaluated. Polynomial models (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    &gt; 0.96,\n                    <jats:italic>p<\/jats:italic>\n                    &lt; 0.001) revealed significant synergistic interactions, particularly between\u00a0\n                    <jats:italic>T. capitatus<\/jats:italic>\n                    \u00a0and\u00a0\n                    <jats:italic>R. officinalis<\/jats:italic>\n                    . Desirability optimization yielded an optimal mixture of 52%\u00a0\n                    <jats:italic>T. capitatus<\/jats:italic>\n                    , 8%\n                    <jats:italic>R. officinalis<\/jats:italic>\n                    , and 40%\n                    <jats:italic>A. citrodora<\/jats:italic>\n                    , which exhibited potent activity (67.81%\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010amylase inhibition, 76.99% DPPH scavenging) comparable to or better than pure\u00a0\n                    <jats:italic>T. capitatus<\/jats:italic>\n                    . Crucially, this optimized blend showed significantly reduced cytotoxicity on Vero cells (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 105.36\u00a0\u00b5g\/mL) compared to\u00a0\n                    <jats:italic>T. capitatus<\/jats:italic>\n                    \u00a0alone (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 82.46\u00a0\u00b5g\/mL) and was over 20\u2010fold safer than doxorubicin (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 5.11\u00a0\u00b5g\/mL). The results demonstrate the efficacy of mixture design in balancing potency and safety, proposing the optimized essential oil blend as a promising low\u2010toxicity candidate for the adjuvant management of diabetes and oxidative stress, warranting further\u00a0in vivo\u00a0validation.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202503735","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T07:16:01Z","timestamp":1775027761000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimized Mixture of Essential Oils From\n                    <i>Thymus capitatus<\/i>\n                    ,\n                    <i>Rosmarinus officinalis<\/i>\n                    , and\n                    <i>Aloysia citrodora<\/i>\n                    : Synergistic Antidiabetic and Antioxidant Activities With Reduced Cytotoxicity"],"prefix":"10.1002","volume":"23","author":[{"given":"Mariem","family":"BenJemaa","sequence":"first","affiliation":[{"name":"Laboratory of Aromatic and Medicinal Plants Center of Biotechnology of Borj Cedria  Hammam\u2010Lif Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarra","family":"Dakhlaoui","sequence":"additional","affiliation":[{"name":"Laboratory of Aromatic and Medicinal Plants Center of Biotechnology of Borj Cedria  Hammam\u2010Lif Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumaya","family":"Bourgou","sequence":"additional","affiliation":[{"name":"Laboratory of Aromatic and Medicinal Plants Center of Biotechnology of Borj Cedria  Hammam\u2010Lif Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Ammar","sequence":"additional","affiliation":[{"name":"Laboratory of Aromatic and Medicinal Plants Center of Biotechnology of Borj Cedria  Hammam\u2010Lif Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarra","family":"Bachkouel","sequence":"additional","affiliation":[{"name":"Laboratory of Aromatic and Medicinal Plants Center of Biotechnology of Borj Cedria  Hammam\u2010Lif Tunisia"},{"name":"Research Support and Technology Transfer Center of Biotechnology of Borj Cedria  Hammam\u2010Lif Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada","family":"Hassine","sequence":"additional","affiliation":[{"name":"Laboratory of Aromatic and Medicinal Plants Center of Biotechnology of Borj Cedria  Hammam\u2010Lif Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4826-8041","authenticated-orcid":false,"given":"Kamel","family":"Msaada","sequence":"additional","affiliation":[{"name":"Laboratory of Aromatic and Medicinal Plants Center of Biotechnology of Borj Cedria  Hammam\u2010Lif Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolo Maria","family":"Ippolito","sequence":"additional","affiliation":[{"name":"Department of Industrial and Information Engineering and Economics University of L'Aquila  L'Aquila Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hsr2.2004"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109119"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573399819666230413094200"},{"key":"e_1_2_8_5_1","article-title":"Comparison of the Efficacy, Tolerability and Side Effect Profile of Vildagliptin\u2010Metformin With Metformin\u2010GlibenclamideMamong Nigerian","volume":"38","author":"Uloko A.","year":"2021","journal-title":"West African Journal of Medicine"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00006"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.9734\/BJPR\/2014\/8382"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2025.141504"},{"key":"e_1_2_8_9_1","first-page":"1","article-title":"Advances in Essential Oils for Metabolic Diseases","volume":"16","author":"Li X.","year":"2025","journal-title":"Frontiers in Endocrinology"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2025.144239"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202500008"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/horticulturae10070684"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants11070954"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.621536"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2019.1631359"},{"key":"e_1_2_8_16_1","article-title":"Essential Oil Composition and Antidiabetic, Anticancer Activity of Rosmarinus officinalis L. 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