Essential oils (EOs) are a diverse source of bioactive compounds with remarkable therapeutic potential. Despite their significance, Conocarpus EOs have been largely underexplored. This study provides a novel comparison of the metabolic profiles and biological activities of EOs from C. lancifolius, C. erectus green, and C. erectus silver leaves cultivated in the United Arab Emirates (UAE), offering unique insights into their distinct bioactive properties and potential therapeutic applications. EOs were extracted via hydro-distillation, analyzed using gas chromatography–mass spectrometry (GC-MS), and subjected to chemometric analysis. Their antioxidant (2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing ability of plasma (FRAP) assays), antidiabetic (α-amylase and α-glucosidase inhibition), acetylcholinesterase (AChE) inhibition and antimicrobial activities were assessed. A total of 92 metabolites were identified, with heptacosane and nonacosane as key species discriminants. C. lancifolius EO showed the strongest α-amylase (IC50 8.75 ± 0.54 µg/mL) and α-glucosidase (IC50 22.31 ± 0.92 µg/mL) inhibitory activities, while C. erectus silver demonstrated superior antioxidant capacity (IC50 349.78 ± 8.26 µg/mL, DPPH assay). C. lancifolius EO exhibited the best antimicrobial activity, particularly against Staphylococcus aureus (MIC 625 µg/mL). C. erectus silver EO inhibited E. coli and C. albicans (MIC 625 µg/mL). In contrast, C. erectus EOs showed no activity against Aspergillus niger. These findings highlight the potential of Conocarpus EOs as antioxidants and for managing diabetes that may be utilized either in nutraceuticals, dietary supplements or even in pharmaceutical formulations. Moreover, owing to significant antimicrobial activities, the EOs may be added to medical disinfectants and several pharmaceutical products. However, further, in vivo validation and pharmaceutical exploration is still needed.
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