Semaglutide (sold under the brand names Mounjaro, Ozempic, Rybelsus, and Wegovy), a glucagon-like peptide-1 (GLP-1) receptor agonist, is clinically used to treat type 2 diabetes, obesity, and cardiovascular disease. As one of the fastest growing treatments for glucose regulation in the United States, it has been attributed to curbing American obesity rates for the first time in over a decade. However, the long-term off-target effects of semaglutide are still poorly understood and require further investigation. In particular, metabolome alteration upon semaglutide treatment has not been comprehensively studied. This review leverages studies within the past decade, seeking to understand the impact of semaglutide on the metabolomic profile of mice. Studies in this review encompass several essential organs and organ systems, including the heart, liver, kidneys, brain, and intestine. This review highlights the anti-inflammatory and protective effects of semaglutide across multiple organs. Additionally, it discusses the optimization of organ-specific metabolic processes, particularly in mice with obesity or related diseases. This review provided valuable insight towards semaglutide's mechanism of action and suggests future research into therapeutic potential for different diseases. Overall, this review presents a comprehensive view into the off-target effects of semaglutide and offers a deeper understanding of its effect on the metabolomic profiles of mice.