Twenty-one new triterpenoid saponins, named caryocarosides (1−21), glycosides of 2β-hydroxyoleanolic acid, hederagenin, bayogenin, and gypsogenic acid, have been isolated from the fruits of Caryocar glabrum along with nine known triterpenoid saponins (22−30) that are described for the first time from a plant in the Caryocaraceae. Their structures were established by 1D and 2D NMR techniques (13C, COSY, TOCSY, HSQC, HMBC, and ROESY experiments), ESIMS, and acid hydrolysis. The isolated compounds could be classified into two series:  glucosides (1−8, 22, 27, and 30) derived from the 3-O-monoglucoside and glucuronides (9−21, 23−26, 28, and 29) derived from the 3-O-monoglucuronide. In 22 of the saponins (1−8, 12−22, and 24−26), a galactose moiety was linked to C-3 of a glucuronic acid or a glucose moiety. The galactose was substituted in position 3 by a second galactose unit (6, 7, 20, and 21) or by a xylose unit (8). Seven saponins (4, 5, 16−19, and 26) were found to be bidesmosides with one glucose unit linked to C-28 of the aglycon. The hemolytic activity of the major saponins (2, 3, 5, 12−15, 17, 24, and 28) was measured on sheep erythrocytes in order to establish structure−activity relationships based on the type of sugar attached to the aglycon and on the structure of this aglycon