Phytochemical investigation on the aerial parts of Zornia diphylla resulted in the isolation and identification of one undescribed triterpenoid saponin, zordiphylloside I (1), together with 25 known compounds. Their structures were elucidated by comprehensive spectroscopic methods, including 1D and 2D NMR and MS. Notably, 24 compounds were isolated from this plant for the first time. Zordiphylloside I showed moderate cytotoxicity against human breast carcinoma cell line (MCF-7) and human prostate cancer cell line (LNCaP), with IC values of 26.52 and 45.37 µM, respectively.