Twelve new megastigmane sesquiterpenoids, wilsonols A-L (1-12), were isolated from the leaves of Cinnamomum wilsonii, along with seven known analogues (13-19). The structures of compounds 1-12 were established by spectroscopic analyses. The absolute configurations of 1-5 were determined by single-crystal X-ray diffraction analysis with Cu Kα irradiation, and the absolute configurations of 6-12 were determined by the modified Mosher's method. Compounds 1-9 and 13-19 were evaluated for in vitro cytotoxicity against five human cancer cell lines, HL-60, SMMC-7721, A-549, MCF-7, and SW-480, and compared against the Beas-2B immortalized (noncancerous) human bronchial epithelial cell line. Compound 13 exhibited IC50 values ranging from 2.5 to 12 μM and selectivity indices of >10 against SMMC-7721, A-549, and MCF-7 cell lines. Selected compounds were evaluated for in vitro immunomodulatory activity.