Three new eremophilane sesquiterpenes, dendryphiellins H-J (1-3), and three new phthalide natural products (4-6) were isolated from the marine-derived fungus Cochliobolus lunatus SCSIO41401. Their structures including absolute configurations were determined by spectroscopic and calculated ECD analyses. Dendryphiellin I (2) showed cytotoxic and antibacterial activities against five cancer cell lines (IC50 1.4 to 4.3 μM) and three bacterial species (MIC 1.5 to 13 μg/mL), respectively. Dendryphiellin J (3), a rare naturally occurring aldoxime analogue, displayed cytotoxicities against ACHN and HepG-2 cells with IC50 values of 3.1 and 5.9 μM, respectively. Further studies indicated that 3 induced apoptosis in ACHN cells in a dose- and time-dependent manner.