Chemical investigation of bioactive components from the whole plant of <i>Euphorbia helioscopia</i> resulted in the isolation and identification of 17 new jatrophane diterpenoids, namely, heliojatrone D (<b>1</b>) and helioscopids A-P (<b>2</b>-<b>17</b>), along with 11 known analogues (<b>18</b>-<b>28</b>). The structural elucidation of the new diterpenoids was achieved by the comprehensive analysis of HRESIMS, NMR, and X-ray crystallographic data, as well as using electronic circular dichroism. Structurally, heliojatone D (<b>1</b>) is the fourth natural diterpenoid with a rare bicyclo[8.3.0]tridecane skeleton. The inhibitory effect of the isolated diterpenoids against Kv1.3 ion channels was evaluated in a human embryonic kidney 293 cell model transfected with plasmid encoding Kv1.3, resulting in the identification of a series of potent Kv1.3 ion channel inhibitors, with the most active ones (<b>2</b> and <b>15</b>) showing IC<sub>50</sub> values of 0.9 μM.