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The aim of the present study was to evaluate and compare the chemical composition, antimicrobial, antiparasitic, and cytotoxic properties of the essential oils extracted from Rhanterium adpressum Coss. & Dur. (EORA) and Rhanterium suaveolens Desf. (EORS). The main compounds of EORA were myrcene (18.51%), α-pinene (14.36%), sabinene (13.55%), β-pinene (5.67%), and camphene (5.39%). While camphene (25.06%), α-pinene (13.14%), myrcene (9.74%), sabinene (8.27%), D-limonene (7.86%), and β-pinene (7.34%) constituted the major components of EORS. A potent antibacterial activity was also recorded against Escherichia coli with MIC = 5.72 mg/mL for EORA and MIC = 5.96 mg/mL for EORS. Concerning the antifungal effect, a remarkable efficiency was exerted against the two tested Candida albicans strains (MIC < 5.96 mg/mL) for EORS and against Candida albicans 26 (MIC = 5.72 mg/mL) for EORA. Furthermore, a promising antiparasitic ability was observed against Acanthamoeba castellanii (IC50 = 6.42±0.21 μg/mL) for EORS and against Leishmania amazonensis (IC50=9.66±1.46 μg/mL) for EORA. However, low cytotoxicity was recorded against macrophages J774-A1 (LC50 = 67.68±4.02 μg/mL) only for EORS. Based on the present findings, it may be concluded that the two tested EOs possess significant antimicrobial and antiparasitic activities with minimal cytotoxicity, so they can be used as new sources of antimicrobial and antiparasitic drugs. [ABSTRACT FROM AUTHOR]