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Three new compounds including a meroterpenoid (<b>1</b>) and two isocoumarins (<b>8</b> and <b>9</b>), together with thirteen known compounds (<b>2–7</b>, <b>10–16</b>) were isolated from the metabolites of <i>Talaromyces amestolkiae</i> MST1-15. Their structures were identified by a combination of spectroscopic analysis. The absolute configuration of compound <b>1</b> was elucidated on the basis of experimental and electronic circular dichroism calculation, and compounds <b>8</b> and <b>9</b> were determined by Mo₂(OAc)₄-induced circular dichroism experiments. Compounds <b>7–16</b> showed weak antibacterial activities against <i>Stenotrophomonas maltophilia</i> with MIC values ranging from 128 to 512 μg/mL (MICs of ceftriaxone sodium and levofloxacin were 128 and 0.25 μg/mL, respectively).