The human microbiome comprises a complicated assembly of microorganisms inhabiting the body and its surfaces. It plays an important role in various physiological functions, such as digestion, immune homeostasis, and disease prevention. The development and improvement of sequencing technologies have advanced our knowledge of these microbial ecosystems and their interactions with host species. Probiotics, prebiotics, and fecal microbiota transplantation are the therapeutic methods in this regard that have been the focus of considerable research regarding their role as a means to alter the microbiome toward better health. Probiotics are preparations of live antibiotic-producing microbes, which favorably affect intestinal barrier integrity, alter the immunologic response of the host, and stimulate the growth of probiotic bacteria. Prebiotics are dietary nondigestible fibers, whose selective fermentation promotes the growth or activity of beneficial bacteria within the gastrointestinal tract, reducing the risk of disease by maintaining gut health. In spite of the fact that it is a very promising technique, with the exception of treatments for Clostridioides difficile infections, most require further studies before general use. The gut microbiome is also highly dependent on diet and lifestyle. Diets high in fiber enhance the abundance of symbiotic bacteria, whereas high-fat diets strongly reduce microbial diversity and increase proinflammatory bacterial species. In addition, regular exercise and sleep are critically important for coping with stressful conditions. Poor sleep and chronic stress degrade microbial communities, leading to dysbiosis. Apart from the potential of such research in microbiomes, other challenges include individual variability and ethical concerns; these are very important to note during translation to the clinic. Ongoing microbiome research holds tremendous promise for personalized health and prevention that deserves to be encouraged toward future treatments and human health.