Nine new highly oxygenated 3,5-dimethylorsellinic acid-derived meroterpenoids, talaromynoids A–I (1–9), were isolated from the marine-derived fungus Talaromyces purpureogenusSCSIO 41517. Their structures including absolute configurations were elucidated by HRMS, NMR, single-crystal X-ray diffraction analysis, and electronic circular dichroism calculations. Compounds 1and 7–9possessed unprecedented 5/7/6/5/6/6, 6/7/6/6/6/5, 6/7/6/5/6/5/4, and 7/6/5/6/5/4 polycyclic systems, respectively. Biologically, compound 5showed selective inhibitory activity against phosphatase CDC25B with an IC50value of 13 μM. Moreover, 7–9and 12exhibited the activity of reducing triglyceride in 3T3-L1 adipocytes in a dosage-dependent manner.