<jats:title>Abstract</jats:title><jats:p>Two new prenylated indole diterpenoids, tolypocladins K and L (<jats:bold>1</jats:bold> and <jats:bold>2</jats:bold>), together with a known analog terpendole L (<jats:bold>3</jats:bold>), were isolated from the solid fermentation culture of a mine soil‐derived fungus <jats:italic>Tolypocladium</jats:italic> sp. XL115. Their structures and relative configurations were determined by comprehensive spectroscopic data analysis, as well as by comparison of their NMR data with those related known compounds. Compound <jats:bold>3</jats:bold> exhibited remarkable antibacterial activity against <jats:italic>Micrococcus luteus</jats:italic> with an MIC value of 6.25 μg/mL, and compounds <jats:bold>1</jats:bold> and <jats:bold>3</jats:bold> displayed moderate antifungal activity selectively against tested strains with MIC values of 25–50 μg/mL.