Fractionation of an EtOAc extract of the roots of <i>Perovskia abrotanoides</i> yielded 28 diterpenoids, including 12 new analogues, <b>1</b>-<b>12</b>. The structures of these diterpenoids were established using comprehensive spectroscopic data analysis, including 1D and 2D NMR, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism spectroscopy, and comparison with literature data. The extract and some of the tested compounds showed significant anti-inflammatory activity on J774A.1 macrophage cells stimulated with <i>E</i>. <i>coli</i> lipopolysaccharide. In particular, the tested compounds significantly inhibited the release of nitric oxide and the expression of related proinflammatory enzymes, such as inducible nitric oxide synthase.