Eleven new chlorinated cyclopentene derivatives, periconsins A-K, and a new diketopiperazine, periconzin, were found from Periconia sp. cultured in three different media by the one strain many compounds strategy. Additionally, the C-1 methyl hydroxylation of chlorinated cyclopentene was found for the first time in the host plant culture. The structures were identified by extensive spectroscopic analyses, electronic circular dichroism (ECD) and 13 C NMR calculations, and single-crystal X-ray diffraction. Compounds 3, 5, 7−11, 15, and 17 showed significant antifungal activities against the plant pathogens Periconia sp., Altemaria sp., and Nigrospora oryzae with MICs ≤2 μg/mL. Other compounds had antifungal activities with MICs ≤8 μg/mL. The antifungal structure−activity relationship of these metabolites indicated that the chlorine at C-5 can increase the activity, but the hydroxy group at C-1 lowered the activity.