In recent years, Akebia trifoliata used to restore rocky desertification environment. We first discovered that the medicinal content of A. trifoliata will increase in rocky desertification habitats, but its mechanism of action is not clear. In this study, A. trifoliata was planted in normal habitats and rocky desertification habitats, and changes in the content of secondary metabolites and related enzyme activities were analyzed. The results showed that: (1) the biomass of the roots, stems and leaf of A. trifoliata reduced significantly, but the content of secondary metabolites increased significantly in rocky desertification habitats. It is mainly reflected in the content of tannins in leaves, flavonoids in roots, and total phenols in roots, stems and leaves. (2) A. trifoliata changed the enzyme activities of PAL (Phenylalanine ammonialyase), C4H (Cinnamate-4-Hydroxylase) and 4CL (4-Coumarate: Coenzyme A Ligase), thereby regulated the increase in the content of secondary metabolites in rocky desertification habitat. (3) the content of medicinal components of A. trifoliata increased significantly in rocky desertification habitat. The highest content of oleanolic acid in the roots from July to August, and the highest content of α-hederagenins in the stems in July; (4) principal component analysis showed that the main response index of A. trifoliata secondary metabolites and related enzymes in rocky desertification habitats was total phenols. This study revealed the response mechanism of A. trifoliata secondary metabolites and related enzymes in rocky desertification habitats. It not only provided a new choice for the exploiting of medicinal resources of A. trifoliata, but also provided a new theoretical basis for A. trifoliata to restore rocky desertification environment.