Three novel phomactin diterpenes neocucurbins A-C (1-3) and their derivatives, neocucurbins D-G (4-7), were isolated from the marine-derived fungus Neocucurbitaria unguis-hominis FS685. Among them, neocucurbins A-C represent the first examples of the phomactin family with an unprecedented skeleton sharing a novel polyoxygen-hetero 5/6/12 or 5/6/13 fused tricyclic ring system; whereas neocucurbins D-G feature a 5/6 fused bicyclic ring system with the opening of the macrocyclic ring, which was found in the phomactin family for the first time. Moreover, spectroscopic data analyses, single-crystal X-ray diffraction experiments, and ECD calculations were conducted to illustrate the absolute configurations of their structures. Furthermore, all seven compounds (1-7) were evaluated for their cytotoxic and antimicrobial activities.