Eleven new cytochalasins, curtachalasins F–P (1–11), were isolated from the rice fermentation of endophytic fungus Xylaria cf. curta. Their structures were identified by extensive spectroscopic methods, X-ray diffraction, and quantum chemistry calculations. Curtachalasin P possesses a unique 5/6/6/7 fused ring system. In the bioactivity screening for curtachalasins F–P, A–C, and E (1–15), compounds 1, 3–6, 8–13, and 15 did not show obvious cytotoxicity against primary mouse splenocytes. Furthermore, the immunosuppressive assay against concanavalin A (ConA) induced T lymphocyte cell proliferation and lipopolysaccharide (LPS) induced B lymphocyte cell proliferation showed that compound 1 results in significant selective inhibition on B-cell proliferation (IC₅₀ value of 2.42 μM) and compound 10 has selective inhibition on T-cell proliferation (IC₅₀ value of 12.15 μM). These interesting immunosuppressive properties of this class of compounds provide new clues to fulfill the urgent demand for new immunosuppressive drugs.