The silkworm, Bombyx mori, has been exploited not only as an economic insect in the silk industry but also as a research model to understand various biological and physiological phenomena. For instance, while there is a concern of bacterial and viral infections leading to substantial losses for the silk producer, B. mori serves as a research model to attain valuable information regarding the mechanism of such infection and consequent resistance. Over the past several decades, many kinds of red fluorescent proteins (RFPs) have been identified in the gut components and/or in the juice of B. mori and were suggested to play a central role in the silkworm immunity. However, the actual mechanism behind the formation of those RFPs and their downstream processing to become bioactive modulators is unclear. Our lab showed that the bioactive RFPs originate due to the formation of a macromolecule complex from the binding of chlorophyllide derived from the daily diet of herbivorous B. mori with their midgut protein. Herein, we give a detailed overview of the RFPs and their metabolites possessing antiviral/antimicrobial capabilities and immunomodulatory properties with a particular emphasis on B. mori-derived 252 kDa red fluorescent protein. Our summary could serve as useful information for the researchers working on characterizing chemical modulators derived from gut epithelium.