Nutraceuticals are defined as products isolated or purified from foods that are generally sold in medicinal or dosage forms not usually associated with food which is demonstrated to have a physiological benefit or provide protection against chronic disease. In this context, the products offered should be rigorously evaluated by international regulatory agencies. More recently, nutraceuticals have been proposed as a potential preventive and therapeutic option in the assessment of chronic diseases, mainly by altering the microbiome composition. However, the current lack of conclusive evidence supporting the "healthy" or "normal" microbiome, along with the dysbiosis concept paradigm, could be both contributing to the lack of homogeneous results. These issues may be solved in the next years with the use of emergent technologies in the individual's microbiome assessment and its fluctuations in time or related to many factors, such as nutraceuticals. Additionally, future research assessing the independent association between the dysbiosis modification and any "potential" nutraceutical product (including bioactive ingredient or chemical compound in food) is going to enlarge the currently reduced "established nutraceuticals" group. In this work we have assessed the nutraceutical's potential role as a microbiome-targeted manipulation therapy, and the gut-liver axis involved in the digestive diseases' pathogenesis and progression, including the chronic liver diseases. Moreover, microbiome targeted nutraceuticals that show consistent results might be further included in clinical research and trials in the therapeutic assessment of chronic diseases. Finally, the indication of these quality microbiome-targeted nutraceuticals will undoubtedly carry health benefits for individuals.