Purpose: To evaluate the anti-cancer potentials of a decoction of Flueggea. leucopyrus (Willd.) on human endometrial carcinoma (AN3CA) cells. Methods: Decoction was prepared by boiling 60 g of the ground plant material in 1.6 L of distilled water for about 3 h to reduce the volume to 200 mL and then freeze dried. The effect of the decoction on AN3CA cells was determined by evaluating its cytotoxicity by 3-(4, 5-dimethylthiazol-2yl) -2, 5-biphenyl tetrazolium bromide (MTT) and sulphorhodamine B (SRB) assays, as well as its ability to modulate apoptosis (microscopic observation of morphological changes, DNA fragmentation and caspase activity). The antioxidant activity of the decoction was also determined by DPPH assay, and its total polyphenolic and flavonoid content. Results: The decoction exerted a significant dose-dependent cytotoxicity on AN3CA cells as evident from MTT assay IC50 values of 22.09 and 14.60 μg/mL at 24 and 48 h post-incubation, respectively; and SRB assay IC50 values of 28.60 and 15.09 μg/mL at 24 and 48 h post-incubation, respectively. The decoction also enhanced apoptosis as shown by enhanced DNA fragmentation, microscopic observation of nuclear condensation, fragmentation and apoptotic bodies and enhanced caspase 3 and 9 activities, as well as moderately increased radical scavenging activity. Conclusion: The cytotoxic and apoptotic effects demonstrated by F. leucopyrus (Willd.) decoction provide supportive evidence for the ethnomedicinal use of this plant for cancer therapy. Keywords: Fleuggea leucopyrus (Willd.), Endometrial carcinoma cells, Cytotoxicity, Apoptosis,Antioxidant, Anti-cancer