New meroterpenoids, meroantarctines A-C (<b>1</b>-<b>3</b>), with unique 6/5/6/6, 6/5/6/5/6, and 6/5/6/5 polycyclic systems were isolated from the alga-derived fungus <i>Penicillium antarcticum</i> KMM 4685. Their structures were elucidated by spectroscopic methods, X-ray diffraction, and quantum chemical calculations. A biogenetic pathway for <b>1</b>-<b>3</b> was proposed. Meroantarctines A-C (<b>1</b>-<b>3</b>) inhibited p-glycoprotein activity and could resensitize drug-resistant cancer cells to docetaxel.