Twelve new hypothemycin-type resorcylic acid lactones, three 10-membered (<b>1</b>-<b>3</b>) and nine 14-membered (<b>4</b>-<b>12</b>), together with seven known analogues (<b>13</b>-<b>19</b>), were obtained from the solid rice-based culture of <i>Podospora</i> sp. G214. Their structures were elucidated utilizing spectroscopic analysis, and the absolute configurations were determined by modified Mosher's method, Mo<sub>2</sub>(OAc)<sub>4</sub>-induced electronic circular dichroism experiments, and single-crystal X-ray diffraction. Compounds <b>1</b>, <b>5</b>, <b>10</b>, and <b>12</b>-<b>19</b> exhibited potent immunosuppressive activities against concanavalin A-induced T cell proliferation with IC<sub>50</sub> values ranging from 6.0 to 25.1 μM and lipopolysaccharide-induced B cell proliferation with IC<sub>50</sub> values ranging from 6.2 to 29.1 μM. Further studies revealed that <b>1</b> induced apoptosis in activated T cells through the JNK-mediated mitochondrial pathway.