Urinary tract infections (UTIs) are primarily attributed to Gram-negative bacteria (GNB), especially Escherichia coli, which is the most prevalent pathogen. Since nearly all UTIs are treated empirically, either without sending the sample for culture or before the culture and sensitivity reports are obtained. Hence, this study aimed to find out the antibiotic susceptibility profile of urinary isolates of E. coli, specifically focusing on fosfomycin and nitrofurantoin. This cross-sectional study was conducted for the period of one year, from 1^st July 2023 to 30^th June 2024, at the Department of Microbiology, Geetanjali Medical College and Hospital (GMCH), Udaipur. A total of 600 E. coli showed a significant bacteriuria from both genders and all age groups, and both outdoor and indoor patients were included. The received urine samples were processed immediately as per the routine microbiological techniques with aseptic precautions. These samples were inoculated onto nutrient agar, blood agar, and MacConkey agar. E. coli were identified based on their colony morphology and routine biochemical tests. The modified Kirby-Bauer disc diffusion method was employed for antimicrobial susceptibility testing. Out of 600 E. coli, 326 (54.33%) were found in females and 274 (45.67%) in males. The age group most frequently afflicted was 61-70 years, 151 (25.16%). The majority of E. coli were from indoor patients, 336 (56%). ESBL production was seen in 396/600 (66.0%), while 454/600 (75.67%) were multidrug-resistant. Maximum susceptibility among antimicrobials was seen in fosfomycin (96.17%), nitrofurantoin (95.83%), and minocycline (93.17%). In the current situation with challenging treatment of UTIs caused by ESBL-producing and MDR E. coli and limited options of antibiotics, fosfomycin and nitrofurantoin are the promising and safe alternatives as oral agents for both outpatient and inpatient therapy.