<jats:p>Asperochramides A – D (<jats:bold>1</jats:bold> – <jats:bold>4</jats:bold>), a new natural product and three new indole diketopiperazine alkaloids, along with seven known analogs (<jats:bold>5</jats:bold> – <jats:bold>11</jats:bold>), were isolated from the ethyl acetate extract of <jats:italic>Aspergillus ochraceus</jats:italic>. Their structures were elucidated by extensive spectroscopic analyses, <jats:styled-content style="fixed-case">ECD</jats:styled-content> calculation, and single‐crystal X‐ray diffraction analysis. Compounds <jats:bold>3</jats:bold> and <jats:bold>4</jats:bold> represent a rare group of indole diketopiperazine alkaloid with a 3‐hydroxyl‐2‐indolone moiety. The <jats:italic>in vitro</jats:italic> anti‐inflammatory effects of compounds <jats:bold>1</jats:bold> and <jats:bold>3</jats:bold> – <jats:bold>11</jats:bold> were investigated by using <jats:styled-content style="fixed-case">LPS</jats:styled-content>‐stimulated murine macrophage <jats:styled-content style="fixed-case">RAW</jats:styled-content> 264.7 cells. Compounds <jats:bold>1</jats:bold>,<jats:bold> 8</jats:bold>,<jats:bold> 10</jats:bold>, and <jats:bold>11</jats:bold> showed potential anti‐inflammatory activities.