Many experimental studies have investigated various treatment options for patients with multiple myeloma; however, bortezomib, lenalidomide, dexamethasone (RVD regimen) is still considered a gold-standard therapy. This regimen can lead to a wide range of side effects, one of which is enterotoxicity. Significantly efficacious enteroprotective interventions have not yet been developed or implemented into clinical practice. This literature review assesses the development of chemotherapy-driven dysbiosis through Toll-like receptors (TLRs) and explores the hypothesis that the gut microbiome could provide significant enteroprotection. A systematic review was performed by utilizing articles published between 2015-2022 from the following databases: Medical Literature Analysis and Retrieval System Online (Medline), PubMed, Science Direct, and Cochrane Library databases. In conclusion, we found further studies of gut microbiome variety and function are necessary and could be used in development of treatment and prevention strategy of chemotherapy enterotoxicity.