Objective: Escherichia coli are the most common pathogenic bacteria to accountable for food and waterborne illness. Therefore, in this way the study was conducted to resolve the occurrence of E. coli bacteria from different water sources in around Tamil Nadu along with to determine their antibiotic resistance profiles. Methods: Water samples were analysed for the presence of E. coli bacteria using specific agar media Eosin Methylene Blue and McConkeys. Colony morphology, Gram staining, various biochemical tests and antibacterial tests performed by disc diffusion method were used to confirm E. coli bacteria. Results: The isolated bacteria were susceptible to Gentamycin (Mullai & Dindigul 18mm) and Tetracycline (Mullai 16mm &Vaigai 18mm) at 37°C for 24 hours. The isolate was susceptible to acetone leaves extract of Abutilon indicum, Calotropis gigantean and Solanum trilobatum in various concentrations (50µl, 75µl, & 100µl) and of A. indicum was most effective inhibition of zone formed in Mullai 24mm, Vaigai 18mm and Dindigul 23mm, triplicate value respectively. Conclusions: In this study revealed that E. coli bacteria were resistant to some antibiotics drugs. Compared to chemical antibiotic, the acetone leaves extract of A. indicum showed excellent inhibition effect (Mullai (24mm), and Dindigul drinking water (23mm) in 100µl concentrations only. But S. trilobatum was showed equal inhibition effect against Vaigai river water (18mm). Therefore, E. coli bacterium was controlled by natural antibiotics of A. indicum and it may reduce the resistance power of food and waterborne illness.