Gut microbiota contributes to diverse mammalian processes including the metabolic functions of drugs. It is a potential new territory for drug targeting, especially for dietary natural compounds such as tan-nins, flavonoids, steroidal glycosides, anthocyanins, lignans, alkaloids, and others. Because most herbal medicines are orally administered, the chemical profile and corresponding bioactivities of herbal med-icines may be altered and implication to ailments by specific microbiota through gut microbiota me-tabolisms (GMMs) and gut microbiota biotransformations (GMBTs). In this review, briefly introducing the interactions between different categories of natural compounds and gut microbiota produced countless microbial degraded or fragmented metabolites with their biological significance in rodent-based models. From natural product chemistry division, thousands of molecules are produced, degraded, synthesized, and isolated from natural sources but exploited due to lack of biological significance. In this direction, we add a Bio-Chemoinformatics approach to get clues of biology through a specific microbial assault to (Natural products) NPs.(c) 2022 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC. All rights reserved. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).