According to outcomes from clinical studies, an intricate relationship occurs between the beneficial microbiota, gut homeostasis, and the host’s health status. Numerous studies have confirmed the health-promoting effects of probiotics, particularly in gastrointestinal diseases. On the other hand, the safety issues regarding the consumption of some probiotics are still a matter of debate, thus to overcome the problems related to the application of live probiotic cells in terms of clinical, technological, and economic aspects, microbial-derived biomolecules (postbiotics) were introducing as a potential alternative agent. Presently scientific literature confirms that the postbiotic components can be used as promising tools for both prevention and treatment strategies in gastrointestinal disorders with less undesirable side-effects, particularly in infants and children. Future head-to-head trials are required to distinguish appropriate strains of parent cells, optimal dosages of postbiotics, and assessment of the cost-effectiveness of postbiotics compared to alternative drugs. This review provides an overview of the concept and safety issues regarding postbiotics, with emphasis on their biological role in the treatment of some important gastrointestinal disorders.