Emerging investigations have indicated that many plant polysaccharides may be beneficial in treating metabolic diseases. Hitherto, the therapeutic efficacies and the potential toxicity of polysaccharides extracted from Clinacanthus nutans (C. nutans) remains unexplored. This investigation studied on the in-vivo acute and sub-acute oral toxicological profile of the highest doses of C. nutans bioactive polysaccharides (CNBP) extracted from leaves using conventional toxicity methods. 39 healthy 8-10 weeks male Sprague-Dawley rats (n=3), were randomly assigned into: control, acute and sub-acute groups receiving 125, 250, 500, 1000, 2000, and 3000 mg/kg/day of CNBP extract respectively; acute groups received a single dose of CNBP extract; whereas the sub-acute groups received daily single doses of CNBP extract for 14 days. Oral administration of up to 3000 mg/kg of CNBP extract caused no abnormal toxicity signs during the 14 days. However, daily administration of 500 mg/kg or higher doses of CNBP extract for 14 days induced a mild degree of toxicity in the liver characterized by elevated alkaline phosphatase levels. The CNBP extracts exhibit therapeutic potential, exemplified by diuretic, natriuretic, anti-hypertensive, anti-tachycardia, reno-protective, and cholesterol lowering properties. Precaution should be taken when administrating the extracts at higher doses and longer durations.