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Immune system modulation is an intriguing part of scientific research. It is well established that the immune system plays a crucial role in orchestrating cellular and molecular key mediators, thus establishing a powerful defense barrier against infectious pathogens. Gut microbiota represent a complex community of approximately a hundred trillion microorganisms that live in the mammalian gastrointestinal (GI) tract, contributing to the maintenance of gut homeostasis via regulation of the innate and adaptive immune responses. However, impairment in the crosstalk between intestinal immunity and gut microbiota may reflect on detrimental health issues. In this context, many studies have indicated that probiotics and their bioactive compounds, such as bacteriocins and short chain fatty acids (SCFAs), display distinct immunomodulatory properties through which they suppress inflammation and enhance the restoration of microbial diversity in pathological states. This review highlights the fundamental features of probiotics, bacteriocins, and SCFAs, which make them ideal therapeutic agents for the amelioration of inflammatory and autoimmune diseases. It also describes their underlying mechanisms on gut microbiota modulation and emphasizes how they influence the function of immune cells involved in regulating gut homeostasis. Finally, it discusses the future perspectives and challenges of their administration to individuals.