Probiotics are live microorganisms known for conferring health benefits through the improvement or restoration of gut microbiota, and tablet is one of the commonly used forms to deliver them. Ensuring the viability of probiotics within tablets is a crucial quality consideration. However, maintaining probiotic viability during tabletting is challenging due to potential lethal mechanisms. Therefore, it is critical to understand the lethal mechanisms behind and determine effective prevention strategies when developing probiotic tablets. In this study, two primary lethal mechanisms are identified during tabletting: mechanical stress and local heating. This review also underscores effective prevention strategies to mitigate their impact during formulation development and the tabletting process. Key approaches include formulation design and process optimisation, encompassing choice of excipient, probiotics/excipients ratio, and compression speed/pressure/profile. By presenting an overview of these lethal mechanisms and corresponding prevention strategies, this paper aims to provide a valuable guideline for the development of probiotic tablets.