Phytochemical investigation of the stems of Cucumis melo led to the isolation and identification of 21 cucurbitane-type triterpenoids, including nine new compounds (1-9) and 12 known compounds. Their structures were determined on the basis of spectroscopic analyses, chemical methods, and comparison with spectroscopic data in the literature. Two known compounds, cucurbitacin B (10) and cucurbitacin A (11), showed significant cytotoxic activity against the proliferation of A549/ATCC and BEL7402 cells in vitro. Of the new compounds, only compound 7 was weakly cytotoxic. The inhibitory effects of all compounds on the Jak-Stat3 signaling pathway were evaluated, but only cucurbitacin B (10) showed significant inhibitory activity of phosphotyrosine STAT3.