Despite discovery of the pathogen more than 100 years ago, tuberculosis (TB) continues to be a major killer disease worldwide. Currently a third of world population is infected and multiple-drug-resistant (mdr) TB registers maximum mortality by a single pathogen. Nanomedicine provides enormous opportunity for developing novel drugs. We have recently demonstrated surface-modified-lipophilic-nanosilica as drug to combat malaria and 100% lethal virus, BmNPV. Nanosilver possesses inherent antibacterial properties, but toxicity is a major concern. We hypothesized that capping with nature-inspired biomolecules, bovine serum albumin (BSA) and Poly-n-vinyl-pyrrolidone (PVP) used as blood volume extender, might insure biosafety. BSA-nano-Ag was found to be more stable than PVP-nano-Ag at physiological pH. In this first ever study on clinical isolates collected from TB endemic areas, we report, BSA-nano-Ag act as potent anti-TB drug. Further study with (human serum albumin)-nano-Ag and core-shell-nano-Ag could increase the biocompatibility of oral TB drug formulations without compromising on the efficacy of the drug.