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This study aimed to evaluate the in vitro anti\u2010<jats:italic>Candida<\/jats:italic> and anti\u2010<jats:italic>Cryptococcus<\/jats:italic> activities of the ethyl acetate fraction (FAAo) from the ethanolic extract of <jats:italic>A. occidentale<\/jats:italic> bark. Ethanolic extract was fractionated and subjected to in vitro cytotoxicity and antifungal activity. After the screening, FAAo was selected for further testing: phytochemical composition, determination of minimum inhibitory concentration (MIC), interaction with fluconazole, kill\u2010curve assay, inhibition of biofilm formation, and experiments to discover the mechanism of action. The liquid chromatography\u2010ultraviolet\/diode array detection\u2010electrospray ionization\/mass spectrometry fingerprint identified phenolic compounds as the majority: catechins, anacardic acids, and cardanols. The FAAo showed a selectivity index ranging between 16 and 32 and MICs &lt; 13 \u00b5g\/mL. There was a synergistic action with fluconazole against <jats:italic>C. tropicalis<\/jats:italic> and <jats:italic>C. neoformans<\/jats:italic>. Although the fungicidal activity of FAAo appears to be a strain\u2010dependent manner, the FAAo is a potential inhibitor of biofilm development by <jats:italic>C. albicans<\/jats:italic> and <jats:italic>C. krusei<\/jats:italic>. The antifungal activity of the fraction appears to be related to the release of proteins and DNA due to lipid peroxidation and binding to ergosterol. The results may provide evidence that this fraction may be a promising source of bioactive compounds useful in combating yeast infections.<\/jats:p>","DOI":"10.1002\/cbdv.202500583","type":"journal-article","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T07:13:36Z","timestamp":1749107616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unveiling the Chemical Composition and the Antifungal Mechanisms of a Phenolic\u2010rich Fraction of <i>Anacardium occidentale<\/i> L. 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