Four new asterosaponins, novaeguinosides A (1), B (2), C (3), and D (4), were isolated from the bioactive fraction of the starfish Culcita novaeguineae, as active compounds capable of promoting polymerization of tubulin. Their structures were elucidated by extensive spectroscopic studies and chemical evidence. Compounds 1 and 3 are characterized by sulfated side chains not previously found in asterosaponins, and 1 is the first example of a trisulfated asterosaponin. In the side chains of 2 and 4, the 26-carboxylic acid function is found as an amide derivative of taurine, which is a rare feature and first encountered among asterosaponins. All the asterosaponins showed cytotoxicity against two human tumor cell lines.