The present study aimed to investigate the effect of Curcuma longa extracts on the drug-resistant Pseudomonas aeruginosa clinical isolates. One hundred urine samples were collected from Qena and Nagaa Hammadi General Hospitals in Upper Egypt. Samples were screened for the prevalence of UTI pathogens by biochemical tests and antibiotics sensitivity. The incidence of the isolated urinary tract infection pathogens in the urine sample was 35% in males and 65% in females patients, represented by age under 30 years (10.77 and 14.29%), from 30 to 60 years (81.54 and 68.57%), and more than 60 years (7.69 and 17.14%) for females and males, respectively. The clinical isolates were Escherichia coli (36%), Klebsiella pneumonia (25%), Pseudomonas aeruginosa (14%), Proteus mirabilis (12%), Enterobacter cloacae (9%), and Acinetobacter baumanii (4%). The ethyl acetate and ethanolic extracts of Curcuma longa showed varying degrees of antibacterial activities against tested clinical isolates ranging from 7 to 18 mm. Further, major compounds of Hydroquinine (47.55%) , Quinine (35.12%) , o-acetyl-L-serine(6.03%), Copaene (37.39%) , Neophytadiene (6.80%) , Phytol, acetate (6.16%), Phytol (38.51%) , 18- Norabietane (5.35%) were determined among 29 bioactive compounds in the aqueous, ethanolic and ethyl acetate extracts of Curcuma longa using gas chromatography-mass spectrometry (GC-MS). These results indicated that the aqueous, ethanolic and ethyl acetate extracts of Curcuma longa have promising antibacterial efficacy against multidrug-resistant bacteria and can effectively deal with the Urinary tract infections.