Oxystelma esculentum is one of the traditional medicinal plant which have been using in treatment of different diseases with less scientific evidence belongs to the family Ascelepiadaceae. In this point of view, the present work carried out to evaluate its anti-tuberculosis, which is the most mortality causing diseases around the world. The qualitative phytochemical analysis was carried out by standard protocols and anti-tuberculosis activity was carried out using Microplate Alamar Blue Assay method on Mycobacterium tuberculosis reference strain H37Rv. The ethanolic extract of O. esculentum flowers showed the positive results for the sterols, phenols, alkaloids, flavonoids, glycosides, tannins and carbohydrates and gave negative result for terpenoids, saponins and oils. The MIC of the extracts which showed inhibitory effect on M. tuberculosis H37Rv was determined at various concentrations of 1, 6.125, 12.5, 25, 50, 100 mg/ml. Accordingly, the MIC of Ethanolic and Aqueous extract O. esculentum in ethanol and water of were 1 mg/ml and 1 mg/ml respectively. So, the present study supports its medicinal u se and further studies on isolation of particular bioactive compounds from O. esculentum are useful.