As a plant used in both food and medicine, <i>Sauropus spatulifolius</i> is consumed widely as a natural herbal tea, food source, and Chinese medicine. Inspired by its extensive applications, we conducted a systematic phytochemical study of the leaves of <i>S. spatulifolius</i>. Thirteen new diterpenoids, sauspatulifols A-M (<b>1</b>-<b>13</b>), including four <i>ent</i>-cleistanthane-type diterpenoids (<b>1</b>-<b>4</b>), eight 15,16-di-<i>nor</i>-<i>ent</i>-cleistanthane-type diterpenoids (<b>5</b>-<b>12</b>), and one 17-<i>nor</i>-<i>ent</i>-pimarane-type diterpenoid (<b>13</b>) as well as one known diterpenoid, cleistanthol (<b>14</b>), were isolated. All of these diterpenoids feature a 2α,3α-dihydroxy unit within the A ring, and their structures were elucidated by spectroscopic data analysis, electronic circular dichroism calculations, and single-crystal X-ray diffraction analysis. Compound <b>14</b> displayed moderate inhibitory activity against <i>Staphylococcus aureus</i>, <i>Staphylococcus epidermidis</i>, <i>Bacillus subtilis</i>, and <i>Shigella flexneri</i> with the same minimum inhibitory concentration value of 12 μg/mL as well as activity against vesicular stomatitis virus and influenza A virus.