Sixteen new (<b>1</b>-<b>16</b>) and three known (<b>17</b>-<b>19</b>) polyacylated <i>ent</i>-kaurane diterpenoid glycosides were isolated from the aerial parts of <i>Inula hupehensis</i>. The planar structures of <b>1</b>-<b>16</b> and their relative configurations were established on the basis of extensive spectroscopic analysis. The absolute configurations of all stereogenic centers for compounds <b>1</b> and <b>6</b> were determined by single-crystal X-ray diffraction experiments, and the absolute configurations of the other new compounds were assigned by chemical degradation and experimental ECD data. Antineuroinflammatory testing of all the isolates showed that compound <b>5</b> inhibited lipopolysaccharide-induced nitric oxide production in BV-2 microglial cells with an IC<sub>50</sub> value of 15.6 μM. In an α-glucosidase inhibitory assay, compound <b>13</b> exhibited a strong inhibitory effect with an IC<sub>50</sub> value of 32.8 μM, whereas the IC<sub>50</sub> value of the positive control, acarbose, was 387.8 μM.