The tryptophan and kynurenine pathway is well-known to play an important role in nervous, endocrine, and immune systems, as well as in the development of inflammatory diseases. It has been documented that some kynurenine metabolites are considered to have anti-oxidative, anti-inflammatory, and/or neuroprotective properties. Importantly, many of these kynurenine metabolites may possess immune-regulatory properties that could alleviate the inflammation response. The abnormal activation of the tryptophan and kynurenine pathway might be involved in the pathophysiological process of various immune-related diseases, such as inflammatory bowel disease, cardiovascular disease, osteoporosis, and/or polycystic ovary syndrome. Interestingly, kynurenine metabolites may be involved in the brain memory system and/or intricate immunity via the modulation of glial function. In the further deliberation of this concept with engram, the roles of gut microbiota could lead to the development of remarkable treatments for the prevention of and/or the therapeutics for various intractable immune-related diseases.