Multidrug-resistant pathogens pose a significant and pressing global health threat. This study explores the therapeutic potential of Indian Traditional Medicine, particularly Yagya, as an innovative antimicrobial strategy rooted in the ancient Rig Veda traditions dating back to 7500 B.C. Our research uses advanced analytical techniques like GC-MS and MALDI-TOF to investigate Yagya's antimicrobial properties against challenging Gram-positive and Gram-negative bacteria. Our study reveals proteomic insights into bacterial responses, including Glutamate Decarboxylase, EF-Tu, and Alpha-Hemolysin. Altered expression levels suggest significant impacts on bacterial survival, shedding light on the multifaceted mechanisms. By showcasing Yagya's remarkable antimicrobial properties, it provides valuable proteomic insights into its mode of action. This study sets stage for future research to harness Indian Traditional Medicine in combatting microbial infections, especially those driven by multidrug-resistant pathogens. This research emphasises the importance of exploring alternative and complementary approaches in modern medicine to combat the global health crisis of antibiotic resistance.