The species Inula Helenium belongs to the genus Inula (Asteraceae) and exhibits antibacterial and anti-inflammatory properties. It is used in respiratory and skin diseases. Its bioactivity is attributed to its eudesmanolide components, mainly to alantolactone and isoalantolactone. These components were isolated in high purity from the plant’s dried roots, either via multiple column chromatography separations or via repeated recrystallization. Two more eudesmanolides structurally similar to their parent compounds, were isolated, namely 11,13-dihydro-alantolactone and 11,13-dihydro-isoalantolactone. The secondary metabolites and their derivatives were characterized in detail, for the first time, via NMR spectroscopy, GC-MS and HRMS.Synthetic modification of the natural component structure was considered necessary for structure-activity relationship studies and biological tests. Thus, each compound was converted to its nitrile and then to the corresponding acid, or to its azide derivative and then corresponding amine. Antioxidant studies were conducted on the parent compounds, their derivatives and the methanolic and hexane plant extracts, using the DPPH radical method. The study revealed a strong antioxidant capacity on the methanolic extract. Acaricidal studies of both, natural products and synthetic analogs against varroa destructor and comparison of their activity with the parent natural product costic acid as well as one of its synthetic congeners indicated that the approach “from nature to synthesis and vice versa” led to active compound as well as to meaningful conclusions regarding the “pharmacophore” groups in the structural framework of the acaricides.