Medoavrutta Spices have become important due to their potential antimicrobial effects. The present work aimed to find out the antimicrobial activity of natural spices on multi-drug resistant Escherichia coli isolated from drinking water. Anti-bacterial potentials of crude extracts Black pepper (Piper nigrum), Coriander (Coriander sativum), Garlic (Allium sativum) and Ginger (Zingiber officinale) were tested against ten Escherichia coli isolated from drinking water sources at Nagpur. Total 28 drinking water samples were analysed, out of which 10 samples were found to be contaminated with E. coli. Isolated E. coli were tested against 8 different antibiotics. It was found that all isolates of E. coli (100%) were found to be resistant to Carbenicillin, Cefuroxime and Amoxyclave while 100% E. coli found to be sensitive to Levofloxacin and Gatifloxacin. Total 90% were sensitive to Azithromycin followed by 80% to Doxycycline Hydrochloride and 50% to Cefixime. When E. coli isolates were tested against 4 spices such as Black Pepper, Coriander, Garlic and Ginger, it was found that 50% E. coli were found to be sensitive to Garlic and Ginger each followed by 40% to Coriander and 30% to Black Pepper.