Antiplasmodial high-throughput screening of extracts derived from marine invertebrates collected from northern NSW, Australia, resulted in the methanol extract of the bryozoan Orthoscuticella ventricosa being identified as inhibitory toward the 3D7 strain of Plasmodium falciparum. Purification of this extract resulted in two new bis-β-carbolines that possess a cyclobutane moiety, orthoscuticellines A and B (1 and 2), three new β-carboline alkaloids, orthoscuticellines C-E (3-5), and six known compounds, 1-ethyl-4-methylsulfone-β-carboline (6), 1-ethyl-β-carboline (7), 1-acetyl-β-carboline (8) 1-(1'-hydroxyethyl)-β-carboline (9), 1-methoxycarbonyl-β-carboline (10), and 1-vinyl-β-carboline (11). The structures of all compounds were determined from analysis of MS and 1D and 2D NMR data. The compounds showed modest antiplasmodial activity against P. falciparum in the range of 12-21 μM.