INTRODUCTION: Gut microbiota produces thousands of metabolites, which have a huge impact on the host health. Specific microbial strains are able to synthesize histamine, a molecule with a crucial role in many physiologic and pathologic mechanisms of the host. This function is mediated by the histidine decarboxylase enzyme (HDC) that converts the amino acid histidine to histamine. AREAS COVERED: This review summarizes the emerging data on histamine production by gut microbiota, and the effect of bacterial-derived histamine in different clinical contexts, including cancer, irritable bowel syndrome, and other gastrointestinal and extraintestinal pathologies. This review will also outline the impact of histamine on the immune system and the effect of probiotics that can secrete histamine. Search methodology: we searched the literature on PubMed up to February 2023. EXPERT OPINION: The potential of modulating gut microbiota to influence histamine production is a promising area of research, and although our knowledge of histamine-secreting bacteria is still limited, recent advances are exploring their diagnostic and therapeutical potential. Diet, probiotics, and pharmacological treatments directed to the modulation of histamine-secreting bacteria may in the future potentially be employed in the prevention and management of several gastrointestinal and extraintestinal disorders.