Actinomycetes are the producer of many secondary metabolites with novel structures and broad biological activities. During our exploration for bioactive compounds from marine-derived actinomycetes, two classes of cytotoxic hybrid isoprenoid alkaloids and six new antifungal polyene-polyols (cultured under shaking condition) have been isolated from the marine-derived Streptomyces sp. CHQ-64. Attracted by the amazing ability of this strain to produce diverse compounds, other fermentation conditions were attempted. Among them, we found that the HPLC-UV profile of the EtOAc extract from the liquid culture under static condition changed markedly. From the broth a new hybrid isoprenoid alkaloid named drimentine I (1) was isolated possessing a rare heptacyclic skeleton formed via two bridging linkages. The planar structure and absolute configuration of 1 were established by a combination of spectroscopic methods and X-ray diffraction analysis. The planar structure and absolute configuration of 1 has been confirmed by a single crystal X-ray diffraction analysis, with the final refinement on the Cu Kα data resulting in a Flack parameter of −0.1, allowing an assignment of the absolute configurations as (3S, 5aS, 10bS, 11aS, 13R, 14R, 16aS, 20aS). Drimentine I (1) represents another rare bacterial terpenylated diketopiperazine with a heavily rearranged heptacyclic skeleton, which was unambiguously assigned by X-ray. Drimentine I (1) were evaluated in vitro for their cytotoxicities against two human tumor cell lines (A549 and HeLa) using the SRB method with adriamycin as positive control. Among these, compound 1 was found to have weak activity against human cervical carcinoma cell line HeLa, with IC50 values of 16.73 μM.