The phytochemicals or secondary metabolites (SMs) discussed in previous chapters confer health benefits, and this chapter summarizes the major mechanisms of action. The general comments made in the previous chapters about the inadequacy of epigenetic studies, incomplete dose-response relationships, or the lack of application of artificial intelligence also apply to studies of the underlying mechanisms. The low dose range of so-called antinutritional factors triggers the adaptive response. Understanding the genetic and epigenetic modes of action of this adaptive response, as well as the role of the gut microbiota in this response, will enable aquacultural scientists to identify individuals with the best adaptation, or learn how to enhance these adaptive processes. Nevertheless, this chapter discusses SM’s improvements in mucosal structure and immunity, as well as its effects on the gut microbiome, which often mirror findings from human nutrition and medicine. It also discusses studies on genes responsible for tolerance to plant diets, transcriptional interactions of macronutrients, and the role of aquaporins.