Two new indole diketopiperazines, namely luteoalbusins A-B (1-2), along with eight known ones (3-10), were isolated from the fungus Acrostalagmus luteoalbus SCSIO F457 originated from deep-sea sediment. Their structures were determined by 1D/2D NMR, MS, and CD data analyses. Each of these compounds was evaluated for their cytotoxic activities against SF-268, MCF-7, NCI-H460, and HepG-2 cell lines, and compounds 1-5 showed significant cytotoxicties against all four cancer cell lines. Moreover, new compounds 1 and 2 had more potent cytotoxicity than the other ones and cisplatin.