Background. The study assessed the toxicity of Ngu-Vi-Tieu-Khat (NVTK), a traditional remedy from the Mekong delta in Vietnam, commonly used by diabetes patients. Its toxicity profile has not been systematically examined before. The objective of the study was to evaluate the single-dose and 90-day repeated-dose oral toxicity of NVTK in Swiss mice and Wistar rats. Materials and methods. The study evaluated single-dose and 90-day repeated-dose oral administration in the two species. In the acute toxicity test, mice were given a single dose of NVTK ranging from 125 to 375 g/kg, then monitored for 7 days for signs of abnormal behavior, toxicity symptoms, weight changes, and death. The sub-chronic toxicity test involved daily doses of NVTK (7.764 and 38.32 g/kg) administered to rats for 90 days. Their behavior, weight, and several organ functions were evaluated. Results. The research showed that NVTK does not produce significant toxicity in mice or rats, even at high doses. There was no indication of single-dose toxicity in mice at the maximum dose of 375 g/kg. Similarly, no mortality or treatment-related adverse effects were observed in rats throughout the 90-day repeated-dose study. The tests, including hematological and biochemical analysis, macroscopic and histopathological examinations, showed normal results, indicating a lack of significant toxicity. Conclusions. The study showed that NVTK decoction extract is safe at high doses as a traditional medicine remedy with a broad therapeutic safety margin. Further research is needed to confirm its safety and benefits for diabetes and other illnesses.