Three new tyramine-type alkamides (<b>1</b>-<b>3</b>), three new natural products (<b>4</b>-<b>6</b>), five new <i>N</i>-acylated/formylated aporphine alkamides with different ratios of rotational isomers (<b>7</b>-<b>11</b>), and 20 known alkamides (<b>12</b>-<b>31</b>) were isolated from an EtOH extract of the stems and leaves of <i>Piper puberulum</i>. The absolute configurations of compounds <b>7</b>, <b>8</b>, and <b>10</b> were determined by single-crystal X-ray diffraction analysis. In the biological activity assay, compounds <b>3</b>, <b>5</b>, and <b>10</b>-<b>23</b> displayed inhibitory effects against lipopolysaccharide-induced NO release in BV-2 microglial cells, exhibiting IC<sub>50</sub> values of 0.93-45 μM.