Five new secoiridoids, gentianopsins A-E (1-5), along with two known analogues (6 and 7) were isolated from the whole plants of the medicinal herb Gentianopsis barbata. Their structures were elucidated by a comparison of extensive spectroscopic analysis (1D and 2D NMR, and HRMS) and quantum chemical calculations. Gentianopsins A (1) and B (2) represented two unusual skeletons of trihomo-secoiridoids. Anti-inflammatory activity of these isolates was evaluated via suppressing the secretion of cytokines TNF-α and IL-6 in LPS-induced macrophages RAW264.7. Significant inhibitory activity was observed for compounds 3 and 7 on IL-6 secretion with IC