The Bacteria with Multidrug resistance and Extreme drug resistance are increasing at a rapid rate. Various methods have been employed to combat drug resistant bacteria. Major classes of antibiotics aren’t effective against these bacteria. Alternative methods have been studied in recent years. Nanoparticles are used against multidrug resistant bacteria; The green synthesized nanoparticles are more reliable due to more shelf life and lesser toxicity relative to chemically synthesized nanoparticles. Multi drug resistant E. coli and Staphylococcus aureus was isolated from sewage samples. Green synthesized nanoparticles from various plants samples have been prepared with Zinc and Copper forming respective oxides with Neem, Nakara, Jatropha, Mango, Clove, Ginger, Cardamom, Cinnamon and Betel against multidrug resistant Escherichia coli and Staphylococcus aureus. Isolated E. coli was susceptible to Fluoroquinolone and Augmentin whereas S. aureus was susceptible to vancomycin. Green synthesized nanoparticles had more antimicrobial activity against E. coli and S. aureus than chemically synthesized nanoparticles and plant extracts. Green synthesized Nakara CuO nano particles had inhibition zone of 31 ±0.6mm and 30 ±0.7mm for E. coli and S. aureus respectively, ZnO nano particles of Nakara had 25 ±0.6mm inhibition zone for E. coli and S. aureus. Green synthesized Jatropha CuO nano particles had inhibition zone of 26 ±0.5 and 26 ±0.4mm for E. coli and S. aureus. ZnO nano particles of Jatropha had 31±0.7mm and 30±0.7mm inhibition zone for E. coli and S. aureus respectively. The Scanning electron microscopy studies revealed 26nm Jatropha ZnO and 25nm Nakara CuO nanoparticles. Nano materials were found to be non-toxic in cell line studies. The present study concludes to study the impact of green synthesized nanoparticles as an alternative to antibiotics to combat multidrug resistant bacteria.