Probiotics are helpful microorganisms that are resistant to biliary, gastric, and pancreatic secretions and can attach to the epithelial cells and colonize the surface of the intestinal cells. These capabilities are the main mechanisms of probiotics that allow them the adaptation to gut conditions. Probiotic cells attach to the intestinal cells and inhibit the attachment of enteric pathogenic germs to the intestinal mucosa by producing growth-inhibitory elements such as short-chain fatty acids, bacteriocin, and toxic oxygen metabolites. Attaching to the mucosal layer is essential for their functions, but it can increase the possibility of translocation and pathogenicity. On the other hand, there are also concerns about the possible transmission of antimicrobial resistance properties from probiotic strains to pathogenic bacteria in the gut environment. Consequently, the use of probiotics is entirely safe only in healthy people, and also it should be used with caution in children, the elderly, pregnant women, and immunocompromised patients. In recent years, scientists take a new approach to using probiotics in a non-viable form (currently known as postbiotics) to overcome the technological, economic, and clinical problems regarding the application of live probiotics. Hence, this chapter provides an overview of the nutritional and clinical concerns caused by probiotic intake in vulnerable patients, with emphasis on the application of a non-viable form of probiotics as a promising alternative.