The human microbiome plays a crucial role in modulating the immune system, influencing both health and disease states. Recent studies have highlighted the potential of microbiome-derived therapies as an innovative approache to harness various immunomodulatory effects. Microbiome-derived metabolites such as short-chain fatty acids (SCFAs) can shape arrays of immune responses. These therapeutic factors also enhance the integrity of the gut barrier, promote anti-inflammatory cytokine production, and modulate T cell differentiation, ultimately leading to improved outcomes in conditions such as autoimmune diseases, neurodegenerative disorders, allergies, infections, and cancer. Clinical trials investigating the use of probiotics, prebiotics, fecal microbiota transplantation (FMT), and phage therapies have demonstrated promising results, indicating a reduction in disease severity and an increase in the quality of life for patients. Challenges pertaining to the need for personalized treatment protocols and a deeper understanding of individual microbiome compositions need to be dealt with more scientific outlook. Future studies should aim to elucidate the specific interactions between microbiota and host immune systems, paving the way for targeted microbiome-based therapies. This chapter underscores the potential of microbiome-derived therapies as a novel strategy for immune modulation, emphasizing the importance of further research to optimize these interventions and explore their application in a broader range of diseases.