<jats:title>Abstract</jats:title><jats:p>Three new prenylated indole alkaloids, including two <jats:italic>β</jats:italic>‐carbolines, penipalines A and B (<jats:bold>1</jats:bold> and <jats:bold>2</jats:bold>, resp.), and one indole carbaldehyde derivative, penipaline C (<jats:bold>3</jats:bold>), as well as two known indole derived analogs, <jats:bold>4</jats:bold> and <jats:bold>5</jats:bold>, were isolated from the deep‐sea‐sediment derived fungus <jats:italic>Penicillium paneum</jats:italic> SD‐44 cultured in a 500‐l bioreactor. The structures of the new compounds were determined on the basis of 1D‐ and 2D‐NMR spectroscopy, as well as by high‐resolution mass spectrometry. The new compounds <jats:bold>2</jats:bold> and <jats:bold>3</jats:bold> showed potent cytotoxic activities against A‐549 and HCT‐116 cell lines.