The whole plant of Leptadenia pyrotechnica afforded 18 new pregnane glycosides (1-18) with sarcostin, 11-hydroxysarcostin, and deacetylmetaplexigenin as the aglycon moieties and acetyl, benzoyl, cinnamoyl, p-coumaroyl, and nicotinoyl ester moieties linked at C-12 and/or C-20 of the aglycon and hexopyranose, 6-deoxy-3-O-methylhexopyranose, and 2,6-dideoxy-3-O-methylhexopyranose sugars linked at C-3 of their aglycon. The structures of these compounds were elucidated by spectroscopic data interpretation and from chemical evidence. The antiproliferative activity of all compounds was evaluated using three continuous murine and human culture cell lines, J774.A1, HEK-293, and WEHI-164. Compounds having deacethylmetaplexigenin as aglycon and a cinnamoyl ester moiety linked at C-12 were the most active constituents.