Five new triterpenoids, including four ursane types (1–4) and one oleanane type (5), together with 15 known ursane types pentacyclic triterpenoids (6–20) were isolated from the fruit spikes of Prunella vulgaris L., a traditional Chinese herbal medicine. Their structures were elucidated based on IR, HR-ESI-MS, and NMR spectroscopic data. The SW579 cell line was used to evaluate anti-thyroid cancer activities of (1–20). The results indicated that (7–9), (16), and (19) exhibited apparent inhibitory activity with IC50 values of 25.73–71.41 μM (cisplatin as positive control, IC50 14.49 ± 0.97 μM). Network pharmacology and molecular docking were also used for the prediction of the synergistic actions and the underlying mechanisms. Accordingly, four potential targets have been characterized.