ABSTRACT: The influence of diet on the gut microbiota is an emerging research area with significant impact on human health and disease. However, the effects of beef, the most consumed red meat in the United States, on gut microbial profile are not well studied. Following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols, the objective of this systematic review was to conduct a rigorous and thorough review of the current scientific literature regarding the effects of beef protein and the resulting bioactivity of beef protein and amino acids on the gut microbiota, with the goal of identifying gaps in the literature and guiding future research priorities. Utilizing MEDLINE Complete, PubMed, ScienceDirect, Scopus, and Google Scholar databases, we conducted searches including terms and combinations of the following: animal protein, amino acid, beef, bioactive compounds, diet, health, microbiome, peptide, processed beef, and protein. We identified 131 articles, from which 15 were included in our review. The effects of beef on mouse and rat models were mostly consistent for the bacterial phylum level. Short-term (1-4-wk) beef intakes had little to no effect on microbial profiles in humans. Most studies utilized high beef feeding (240-380 g/d), and no study examined recommended amounts of protein [?3.71 oz/d (105 g/d) meats, poultry, and eggs, or ?26 oz/week (737 g/wk) from these food sources] according to US dietary guidelines. Additionally, the majority of animal and human studies with adverse findings examined the impact of beef in the context of a diet high in fat or sugar. In conclusion, an extensive gap exists in the literature regarding beef and the microbiota. More studies are necessary to elucidate the role of the microbiota following the consumption of beef, especially in interaction with other dietary compounds, and how beef preparation, processing, and cooking methods differentially influence the biological effects of beef on human health.