<p><i>Ammodaucus leucotrichus</i> is an important medicinal plant with several uses in traditional medicine. The study aimed to investigate the antihyperlipidemic activity of Hairy cumin (<i>Ammodaucus leucotrichus</i>; <i>A. leucotrichus</i>) essential oil (EO). The effect of <i>A. leucotrichus</i> fruit EO (50 and 250&#xa0;mg/kg) on lipid and lipoprotein levels was evaluated on Triton WR-1339-induced hyperlipidemia in rats. Furthermore, the chemical analysis was performed by gas chromatography-mass spectroscopy (GC–MS). In addition, the toxicity assessment was conducted in vivo and in silico. Administration of Triton WR-1339 (200&#xa0;mg/kg) resulted in significant increases in hyperlipidemia-associated parameters, including lipid profile and atherogenic indices. However, pretreatment with <i>A</i>. <i>leucotrichus</i> EO for 7&#xa0;days demonstrated a notable preventive effect against the elevation of lipid levels and atherogenic indices compared to the group subjected solely to Triton WR-1339. The phytochemical composition of the EO revealed the predominant presence of oxygen-containing monoterpenes (55.67%), monoterpene hydrocarbons (29.32%), and oxygen-containing sesquiterpenes (8.03%). The main constituents of <i>A. leucotrichus</i> fruit EO were <span>l</span>-perillaldehyde (46.81%), <span>d</span>-limonene (23.84%), and bornyl angelate (6.20%). Additionally, acute toxicity assessment revealed the absence of adverse effects or mortality caused by the EO, with the estimated acute lethal dose 50 (LD₅₀) exceeding 2&#xa0;g/kg. The study demonstrates the antihyperlipidemic potential of <i>A</i>. <i>leucotrichus</i> EO in an acute hyperlipidemia model. The phytochemical analysis revealed that the predominant constituents of EO were <span>l</span>-perillaldehyde, <span>d</span>-limonene, and bornyl angelate. Finally, the toxicological analysis showed the relative safety of <i>A</i>. <i>leucotrichus</i> essential oil in rats.</p>