Next-generation probiotics (NGPs) represent an innovative group of beneficial bacteria that are currently undergoing research and development. NGPs are designed not only for conventional use as foods or dietary supplements but are also tailored for pharmaceutical applications. Research indicates that NGPs show therapeutic promise in addressing various chronic ailments. Offering multiple advantages over conventional probiotics, NGPs present opportunities for personalized probiotic therapies, involvement in synthetic biology and gene editing, participation in combination therapies, targeted delivery methods, and application in therapeutic settings. Our review discusses the potential therapeutic effect of the NGPs, covering diverse research trajectories for NGPs, including their identification, characterization, and targeted delivery. Furthermore, this review elucidates the influence of NGPs on critical aspects of human health, specifically, gut health, immune function, and broader health outcomes. Mechanistic insights encompass the production of bioactive compounds, competitive interactions with pathogenic bacteria, the modulation of immune cell activity, and the reinforcement of the gut barrier. What is noteworthy is that the current review points out the prevalent NGP strains and their diverse sources, providing a highlight for the comprehensive framework for understanding their potential applications and their future benefits in the domain of advanced therapeutics.