Nine new glucosyloxybenzyl 2-hydroxy-2-isobutylsuccinates, pleionosides M-U (<b>1</b>-<b>9</b>), and 12 known compounds (<b>10</b>-<b>21</b>) were isolated from the pseudobulbs of <i>Pleione yunnanensis</i>. Their structures and absolute configurations were established through a combination of HRESIMS and NMR data and supported by physical and chemical methods. Compounds <b>5</b>, <b>6</b>, <b>10</b>, and <b>15</b> showed significant in vitro hepatoprotective activity against d-galactosamine (d-GalN)-induced toxicity in HL-7702 cells with increasing cell viability by 27%, 22%, 19%, and 31% compared to the model group (cf. bicyclol, 14%) at 10 μM, respectively. Compounds <b>4</b>, <b>9</b>, and <b>11</b> exhibited moderate hepatoprotective activity against <i>N</i>-acetyl-<i>p</i>-aminophenol (APAP)-induced toxicity in HepG2 cells with increasing cell viability by 9%, 16%, and 12% compared to the model group (cf. bicyclol, 9%) at 10 μM, respectively.