Ficus carica is an Asian species of flowering plant belonging to the genus Ficus of the family Moraceae, native to Western Asia and the Middle East. Its fruits, usually known as common fig or fig, have been consumed as a very popular health-promoting fruit worldwide since ancient times. To investigate the potential health-promoting chemical constituents of the fruits of F. carica, a systematic phytochemical study on its fruits was therefore carried out. In our study, four new structurally diverse prenylated isoflavone derivatives, ficucaricones A-D (1-4), along with 12 known analogues (5-16) were separated from the fruits of F. carica. Their chemical structures were ambiguously elucidated based on extensive spectroscopic methods. The anti-inflammatory effects and antiproliferative activities of these isolated prenylated isoflavone derivatives were tested. Prenylated isoflavone derivatives (1-16) displayed remarkable inhibitory effects against nitric oxide (NO) production with the IC₅₀ values ranging from 0.89 ± 0.05 to 8.49 ± 0.18 μM, comparable to that of the positive control (hydrocortisone). Furthermore, compounds 1-16 also exhibited pronounced antiproliferative activities against diverse human cancer cell lines in vitro, holding the IC₅₀ values ranging from 0.18 ± 0.03 to 18.76 ± 0.09 μM. These findings indicate that regular consumption of the fruits of F. carica may help to prevent the occurrence of inflammatory diseases and tumors. Moreover, the isolation and characterization of these prenylated isoflavone derivatives possessing remarkable anti-inflammatory effects and antiproliferative activities could be meaningful to the discovery of new anti-inflammatory and antitumor agents.