Terpenes are hydrocarbons in essential oils and waxes, built from polymerized isoprene units. Ruzicka elucidated and synthesized musk compounds such as cyclopentadecanolide containing polymethylene rings, as well as sesquiterpene and diterpene structures. He also pioneered the chemistry of poly-isoprenoid chains that become precursors of vitamin A and coenzyme Q, greatly advancing natural-product synthesis and the fragrance industry.

By applying ring-contraction reactions of macrocyclic polymethylenes and Baeyer–Villiger oxidation, Ruzicka achieved the first total syntheses of cyclopentadecanone and musk acetate. He proposed the “Ruzicka rule of isoprene skeletons,” correlating the length of polymethylene chains (C_nH_2n−(CH_2)) with odor. His work paved the way for the geraniol→vitamin A synthetic route and provided chemical evidence for the squalene→steroid biosynthetic hypothesis, forming a foundation for modern polyprenoid biosynthesis research.

Ruzicka isolated macrocyclic ketones (C_15–C_17) from Tonkin deer musk and utilized Zn-Cu couple coupling to demonstrate their cyclic nature, refuting earlier acyclic proposals. He formulated the biogenetic isoprene rule and, via oxidative degradation and allylic rearrangements, determined configurations of humulene, caryophyllene and abietic acid. His laboratory developed large-scale methylcyclohexanone condensation routes to produce nitromusk fragrance analogs, influencing perfumery chemistry. Furthermore, his partial synthesis of β-ionone to retinol provided the first semi-synthetic access to vitamin A and underscored the polyprenyl pathway to steroids, later confirmed enzymatically. These insights catalyzed both industrial musk production and biosynthetic investigation of terpenoids and polyisoprenoids.