<p>Diterpenoids from the Euphorbiaceae family are gaining increasing attention due to their diverse pharmacological activities and considerable potential as active ingredients. Diterpenoids from <i>Euphorbia lathyris</i> have emerged as a focal point in natural drug development. Previous studies have documented the ethnopharmacological applications of <i>E. lathyris</i> while providing analyses of its phytochemistry, pharmacokinetics, pharmacological properties, and toxicological profiles. However, systematic reviews critically evaluating the structural diversity, pharmacological activities, and derivatization approaches of <i>E. lathyris</i>-derived diterpenoids remains scarce. Therefore, the main content of this review is to summarize the most recent research reports on diterpenoids isolated from <i>E. lathyris</i> up to now, including structural features, pharmacological activity and structural derivatization of the diterpenoids isolated from the plant, and to summarize the structure–activity relationships (SAR) and the derivatization methods being used for the confirmation of the action targets of the compounds. In addition, this article discusses the nuclear magnetic resonance (NMR) regularities of lathyrane diterpenoids with a <i>Z</i>-Δ¹² double bond, which provides a reference for structure elucidation.</p>