Five new indole-terpenoids named penerpenes E-I (<b>1</b>-<b>5</b>), along with seven known ones (<b>6</b>-<b>12</b>), were isolated from the marine-derived fungus <i>Penicillium</i> sp. KFD28 from a bivalve mollusk, <i>Meretrix lusoria</i>. The structures of the new compounds were elucidated from spectroscopic data and ECD spectroscopic analyses. Compound <b>1</b> was assigned as an indole-diterpenoid with a unique 6/5/5/6/6/5/5 heptacyclic ring system. Compound <b>2</b> represents an indole-diterpenoid with a new carbon skeleton derived from paxilline by the loss of three carbons (C-23/24/25). Compound <b>3</b> contains an additional oxygen atom between C-21 and C-22 compared to paxilline to form an unusual 6/5/5/6/6/7 hexacyclic ring system bearing a 1,3-dioxepane ring, which is rarely encountered in natural products. Compounds <b>1</b>, <b>2</b>, <b>4</b>, and <b>6</b> showed inhibitory activities against protein tyrosine phosphatase 1B (PTP1B) with IC<sub>50</sub> values of 14, 27, 23, and 13 μM, respectively.