Phytochemical investigations of an extract of the aerial parts of Rydingia persica led to the isolation of 14 labdane-type diterpenoids, of which compounds 1 – 5 , 8 , and 12 – 14 turned out to be new natural products, while the remaining compounds were isolated for the first time from the genus Rydingia . Their structures were elucidated using 1D- and 2D-NMR and mass spectrometry, and their absolute configurations were determined by quantum chemical calculation methods. Furthermore, DP4+ NMR chemical shift probability calculations were performed for compounds 12 – 14 , in order to elucidate the orientation of the ambiguous chiral center at C-15, prior to absolute configuration determination. The methanol extract of the aerial parts of R. persica along with subfractions obtained and selected isolated compounds were evaluated for their effects on inflammation-related factors such as nitrotyrosine formation, IL-6 release, and TNF-α release, along with tight-junction proteins claudin-1 and occludin expression in LPS-stimulated HaCaT cells. Occludin and claudin-1 are tight-junction proteins, which play a pivotal role in wound repair mechanisms. Overall, the subfractions and compounds isolated showed moderate to high activity, indicating that labdane-type diterpenoids contribute to the anti-inflammatory and wound-healing activity of R. persica .