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The current study was aimed to evaluate the protective and curative effect of aqueous extract of edible desert truffle specie (Terfezia boudieri) against rat's liver and kidney injuries induced by paracetamol (PCM). Terfezia boudieri was genetically identified by PCR and then sequencing (Genbank NCBI: LT718236.1). Terfezia boudieri aqueous extract (TBAE) was characterized by antioxidant capacity evaluated by 1,1-diphenyl-2-picryl-hydrazyl test (EC50 = 0.415 mg/ml). LC-MS analysis shows that TBAE contains several actives biomolecules such as B3 vitamin (2.73 +/- 0.3 mg/100g dm), quinic acid (2 +/- 0.22 mg/100g dm), chlorogenic acid (0.18 +/- 0.02 mg/100g dm) and quercetin-3-o-rhamonoside (0.09 +/- 0.01 mg/100g dm). Liver and kidney Biochemical parameters showed no significant variation in rat's plasma treated with PCM and/or TBAE. However, the histological studies showed that the liver injuries induced by PCM were characterized by hemorrhage and inflammation. The pretreatment by TBAE showed preservation of normal liver and kidney architecture, this finding suggests its protective effects on these two organs. The co-treatment by TBAE reduced the PCM hepatotoxicity proved by normal central vein and small vacuols. In addition, TBAE reduced kidney PCM toxicity proved by less area inflammation and normal glomerulus. Therefore, TBAE is promoting eventual protective and curative drug against acute toxicity.