<jats:p>On the basis of the one strain–many compounds strategy, five compounds including two new holomycin derivatives <jats:bold>2</jats:bold> – <jats:bold>3</jats:bold>, two new cyclopropaneacetic acid derivatives <jats:bold>4</jats:bold> – <jats:bold>5</jats:bold>, together with one known compound holomycin (<jats:bold>1</jats:bold>) were isolated from a marine‐derived bacterium <jats:italic>Streptomyces</jats:italic> sp. DT‐A37. Their structures were elucidated using NMR and HR‐ESI‐MS analyses. All these compounds were evaluated for their antimicrobial activity, cytotoxic activity, and inhibitory activity against BRD4 protein. Compound <jats:bold>1</jats:bold> exhibited potent cytotoxicity against H1975 cells with <jats:italic>IC</jats:italic><jats:sub>50</jats:sub> value of 1 μ<jats:sc>m</jats:sc>, and its minimal inhibitory concentration values against <jats:italic>Escherichia coli</jats:italic> and <jats:italic>Staphylococcus aureus</jats:italic> were both 64 μ<jats:sc>m</jats:sc>.