Despite the availability of numerous drugs and other therapeutic modalities, the prevention and cure of
over- and under-nutrition triggered metabolic and other disease states continues as a major challenge for
modern medicine. Such silently progressing and eventually life-threatening diseases often accompany
diverse spectrum of comorbid psychiatric disorders. Majority of the global population suffering from
metabolic diseases live in economically developing or underdeveloped countries, where due to
socioeconomic, cultural, and other reasons, therapies may be unavailable. Evidence from preclinical,
clinical, and epidemiological studies of numerous structurally and functionally diverse secondary
metabolites of plants suggest that many of these could be promising therapeutic leads for the treatment
and prevention of malnutrition-associated diseases and mental health problems. The review discusses
the potential therapeutic uses of secondary plant metabolites and their bacterial and mammalian
catabolites based on their bioactivity profiles, with special emphasis on their modulating effects on gut
microbial ecology and physiological stress responses. Based on concepts in medicinal chemistry and
pharmacology considerations that evolved during the author's interactions with David Triggle, secondary
plant metabolites may represent an alternative and economically feasible approach to new drugs.