The antifungal activities of eleven C21-steroidal compounds isolated from Cynanchum wilfordii, together with thirty-six derivatives of caudatin and qingyangshengenin were evaluated on Sclerotinia sclerotiorum and other five fungal strains by the mycelium growth rate method. Four derivatives 1k, 1y, 10d, and 10j exhibited much stronger inhibitions on growth of S. sclerotiorum with IC50 values of 0.0084, 0.0049, 0.0053, and 0.0034 μM, respectively.