Background: Teucrium polium (TP) is a medicinal plant with a long history of consumption as a folk remedy for curing many diseases, including diabetes, common cold, obesity, anxiety, etc. Objectives: The present study aimed at investigating the effects of TP crude extracts (TPCE), as well as its diethyl ether (DE) and petroleum ether (PE) fractions, on the brain, kidney, and liver tissue of male rats in the subchronic phase. Methods: In the study, 45 adult male Wistar rats were randomly assigned to five groups as the PBS (receiving phosphate buffer saline), vehicle (receiving dimethyl sulfoxide), as well as CE, PE, and DE receiving 3 mg/kg (100 µL) TPCE, PE, and DE, respectively, for six weeks. Histopathological examinations by hematoxylin and eosin staining investigated morphological changes in all specimens. Also, the brain samples were stained by the immunohistochemistry (IHC) technique with Ki-67, CD31, p53, Nestin, and GFAP markers. Results: The findings showed that the prolonged consumption of TP caused the formation of histological lesions as apoptosis, degeneration, cytoplasmic vacuolization of neurons, and foamy cells in the brain. The liver, displayed cytoplasmic vacuolization, apoptosis, degeneration, and dilated sinusoids. Moreover, TP led to atrophy, vacuolization, and necrosis in renal cells. IHC studies evidenced an increase in the expression of P53, whereas the expression of Ki67 and CD31 decreased. It should be noted that TP crude extract and fractions were toxic; however, the PE fraction was more cytotoxic than others. Conclusions: The study findings indicated that long-term administration of a sublethal dose of TP impairs cellular integrity in vital orangs, including the liver, brain, and kidney, through triggering the cell death mechanisms.