[Abstract] Natural truxillic and truxinic acid derivatives are interesting cyclobutane dimers, with different stereo

conformations formed by the orientation of groups on the cyclobutane. These derivatives are currently obtained

by connecting different groups through C, O, and N bond condensation at the carboxyl position. Flavonoids,

alkaloids, iridoids, sugars, benzene derivatives, amides, amino acids, lignan groups, and alicyclic organic acids

are mainly included in this group. Therefore, these compounds have diverse and complex structures. Truxillic acid

and truxinic acid derivatives show multiple bioactivities, including anti-inflammatory, analgesic, anti-diabetes,

anti-obesity, anti-hypertensive, anti-cancer, neuroprotective, and hepatoprotective effects, among others. These

derivatives have attracted the attention of Chinese and international researchers due to their unique structures and

bioactivities. These derivatives are considered to be potential and promising natural candidates for the development

of new drugs for many diseases, and also potential parent skeletons for the development of lead compounds with

high activity, high targeting and high selectivity, which endows these derivatives with important applications in

new drug discovery.Therefore, some useful reference in the research and development of truxillic and truxinic acid

derivatives and drug discovery is provided by the configurations, source, bioactivities, and quality analysis of these

derivatives which are systematically summarized and analyzed in this paper.

[Key words] Truxillic acid; Truxinic acid; Cyclobutane compounds; Structural diversity; Bioactivity