<p>Epidemiological studies indicate that modern lifestyle choices are closely linked to the global rise in chronic inflammatory diseases. While considerable research has explored the role of the microbiome in inflammation, a definitive causal relationship has yet to be established. Intestinal epithelial cells (IECs) play a critical role in maintaining a protective barrier that prevents the translocation of harmful molecules and pathogens. Any disruption or compromise to the integrity of these cells can impair this barrier function, facilitating the entry of potentially harmful substances and microorganisms, which subsequently triggers acute inflammatory responses. Microbial dysbiosis is one of the most prominent outcomes of inflammation in the gut, and various therapeutic strategies are currently under investigation to address this imbalance. Among these, probiotics have demonstrated potential in modulating immune and inflammatory responses by altering the composition of the gut microbiota. However, findings from preclinical and clinical studies suggest that probiotics may interfere with the re-establishment of native microbial communities and, in some vulnerable individuals, may even aggravate inflammation. In contrast, postbiotics bioactive compounds produced during the fermentation process by probiotics are emerging as a promising and safer alternative. Increasing scientific evidence supports their beneficial biological effects. In this review, we aim to discuss the most recent findings regarding the anti-inflammatory and immunomodulatory properties of postbiotics, with particular emphasis on key parental probiotic strains.</p> Graphical abstract <p></p>