Dog's mercury (Mercurialis perennis L.) is an old medicinal plant, nowadays used in complementary medicine. Aqueous fermented extracts of the plant are being mainly applied in remedies to treat external inflammations, but a thorough phytochemical characterization is still lacking. Therefore, the conversion of characteristic compound classes from M. perennis extracts during fermentation and storage was investigated. The microbial transformation of the two main depsides phaselic acid (=(2R)-O-[(E)-caffeoyl]malic acid; 1) and mercurialis acid (=(2R)-[(E)-caffeoyloxy]glutaric acid; 2) was monitored by HPLC-DAD. The degradation followed a second-order kinetic, and the calculated half-life periods of both constituents were 67 and 30 months, respectively. Several depside metabolites were detected by GC/MS in AcOEt extracts as tBuMe2Si (TBDMS) derivatives after derivatization, mainly dihydrocinnamic acids. Moreover, numerous α-hydroxy acids were found, allegedly as degradation products from amino acids or peptides. The microbial alteration of the main alkaloid hermidin was also examined. After three days of fermentation, three novel N-metabolites were formed and thoroughly assigned in CH2Cl2 extracts as a mixture of 3-ethylhermidin, 3-ethylhermidin quinone, and (E/Z)-3-ethylidenehermidin by GC/MS and NMR methods, as well as by means of total synthesis. A mechanism for the formation of these N-metabolites starting from dimeric hermidin oxidation products is proposed. The obtained results reveal the complex pathways plant constituents may undergo during the fermentation of the extracts. Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.