Misuse and overuse of antibiotics results in widespread multi-drug resistance. The major cause of increased mortality and morbidity rates is Multi-drug resistance to antibiotics and it becomes a global heath challenges now a days, therefore it becomes a necessity and need for researchers to seek for alternative and natural sources of antimicrobials. In the present study an experimental trial (In-vitro and In-vivo) was undertaken to examine the antibacterial activity of extracts of Swertia chirata leaf against multi drug resistant (MDR) E.coli and S.aureus. Broth dilution test for MIC and Disc diffusion method for antimicrobial susceptibility test were applied to investigate Antibacterial activity of plant methanolic extracts. Twenty five albino mice weighted between 180-200g were used for bacterial inhibitory activity (In- Vivo). Plant extract showed broad spectrum of antibacterial activity against S.aureus in comparison to E.coli and showed MIC values of 20µg/ml. Swertia chirata plant extract contains lesser inhibition zone against E. coli (8.7±0.80) and showed highest zone of inhibition against S.aureus (16.2±0.60). It can be concluded that Swertia chirata plant extract was significantly better (P<0.05) against S.aureus than E. coli. The number of bacteria in treated groups was very low, These findings have cleared demonstrated that the clearance of bacteria from the blood of infected mice by subMIC of plant extract was significant. the findings of present study provide a suitable evidences for the use of a drug composed of plant extract as a new generation of drugs to attack the antibiotic resistance of bacteria.