The human microbiota inhabits diverse microorganisms at different locations inside the body contributing to a complex but stable ecosystem. Among them, the microbiota present in the gut are most studied, because of their involvement in different signalling mechanisms for the maintenance of health. Dysbiosis, an imbalanced gut microbiota, is linked to various diseases, underscoring the importance of the well-balanced microbial system. Their bidirectional communication with different organ systems influences neurological, metabolic and immune responses. The advanced techniques have underlined the potential of microbiota-driven precision therapies to revolutionize treatment across various clinical domains. It is a novel and transformative approach in medicine, utilizing the associations between microbiota and health for the personalized treatment. Based on the individual’s genetic and microbiome profiles, microbiota-precision treatment optimizes the therapeutic outcomes by maximizing the efficacy and minimizing the drug toxicity. This chapter will focus on the emergence of the therapeutic utility of gut microbiota in immune-mediated disorders, gastrointestinal complications and oncology. The microbiota and immune system interplay is also discussed for comprehending their role in inflammatory and immune-mediated disorders. However, microbiota-based precision therapy, while promising, is still an emerging field with significant challenges. These include identification of microbial strain, regulatory approvals and other challenges as well. Finding solutions to the above challenges is crucial to optimize microbiota-precision therapies, and formulating a comprehensive roadmap is needed to guide the development of these therapies, ensuring they can fulfil their therapeutic potential in a safe and effective manner.