Crohn's disease (CD) and Ulcerative colitis (UC) are grouped as Inflammatory Bowel Diseases (IBD). The IBD is associated to a multifaceted interplay between immunologic, microbial, genetic, and environmental factors. Nowadays, the gut microbiota (GM) dysbiosis has been indicated as a cause in the IBD development, affecting the impaired cross-talk between GM and immune cells. Moreover, recent studies have uncovered a crucial role for bacterial post-biotics (metabolites) in the orchestration of the host immune response, as they could be messengers between the GM and the immune system. In addition, transgenic mouse models showed that SCFAs (Short Chain Fatty Acids) and Tryptophan (Trp) post-biotics play important immunomodulatory effects, regulating both innate and adaptive immune cell generation, their function and trafficking. Here, we present an overview on the main microbial post-biotics and their effects on the gut mucosa with specific emphasis on their relevance for IBD. Finally, we discuss the therapeutic potential of SCFA and Trp post-biotics on IBD through approaches based on the “immunonutrition,” defined as a modulation of the immune system provided by specific interventions that modify dietary nutrients.