Metabolomics is an advanced and emerging field in the biological sciences that provides a comprehensive understanding of biological systems’ small molecules (metabolites). This technique has been advanced over the last decades and has drawn much interest from the medical community due to its unique ability to identify biomarkers associated with specific diseases and elucidate the biochemical basis of several diseases . Metabolomics techniques seem to be heading toward significant experimental and practical development, especially in the field of diagnostics. Nuclear magnetic resonance (NMR), mass spectrometry (MS), and chromatography methods identify metabolites in cells, tissues, feces, saliva, and urine samples. Most importantly, metabolomics makes it easier to analyze metabolites in huge amounts, which makes early and precise disease detection possible. Its use in clinical settings is crucial for detecting metabolic trends associated with a diversity of diseases, enabling early diagnosis and personalized treatment. Through the identification of associated biomarkers that indicate the presence and variability of disease, this method is crucial to the diagnosis of several diseases. In this chapter, we discuss the clinical application of metabolomics approaches in infectious diseases, including viral (AIDS, COVID-19, hepatitis B, and hepatitis C) and bacterial (tuberculosis and Clostridium difficile), along with future perspectives.