Tuberculosis (TB) is one of three major infectious diseases, and the control of TB is becoming more difficult because of the emergence of multidrug-resistant and extensively drug-resistant strains. Global metabolite analysis is a powerful tool for understanding host-pathogen interactions. In this study, we explored transcriptomic-based global metabolic profiling of TB using Mycobacterium tuberculosis (Mtb)-infected macrophages. Global metabolite profiling can be effectively used to investigate metabolic changes in both target and remote systemic TB organs in MTB-infected models. Here, this study demonstrates for the first time that the responses to metabolic changes in virulent Mtb H37Rv and avirulent Mtb H37Ra-infected murine bone marrow-derived macrophages. The Mtb H37Rv-induced higher levels of glycolysis pathway and subsequently, intracellular survival in macrophages, as compared with Mtb H37Ra. Furthermore, Mtb H37Ra-induced mitochondria-related function and activity was significantly increased compare with Mtb H37Rv. In this aspect, this study will help in adding up our understanding in TB biology and additionally in the development of new therapeutic approach to reduce TB pandemic worldwide.