A new clerodane diterpene, Caseargrewiin M (1), and one known compound (2) were isolated from fresh ripe fruits of Casearia grewiifolia. The structures of all isolated compounds were evaluated on the basic 1D (1H and 13C) and 2D NMR (COSY, HSQC, HMBC and NOESY) spectral data. All compounds were examined cytotoxicity with five human cancer cell lines, Hep-G2 (hepatocarcinoma), SW620 (colon adenocarcinoma), Chago-K1 (undifferentiated lung carcinoma), KATO-III (gastric carcinoma), and BT474 (breast ductal carcinoma). Isolated compounds showed broad cytotoxicity against five human cancer cell lines with IC50 values between 0.90–6.30 μg/mL.