Typhoid fever is one of the most commonly disseminated diseases and is considered to be linked to poor sanitation. It is responsible for 2-5% of all deaths, and its causative agent is Salmonella typhi. The current study aimed to investigate the antibacterial activity of prebiotics (inulin and starch) and probiotics against multidrug resistance of S. typhi bacterial isolates. Determination of the inhibitory effect of probiotics and prebiotics against S. typhi isolates was performed by agar well diffusion method and minimal inhibitory concentration. Body samples of all eligible patients were collected and cultured. Finally, 50 (25%) out of the total cultured samples were S. Typhi bacteria isolated from different samples. The bacteria were mainly found in blood, followed by stool and fluid (74%, 24%, and 2%, respectively). On differential medium, xylose lysine deoxycholate agar, the colonies appear red with black centers, while on MacConkey agar, the colonies appear smooth, pale, transparent, colorless, and raised. Regarding the inhibition zone values of bacteriocins of Lactobacillus from Yogurt against S. typhi in plate, significant differences were identified between the ones with and without prebiotic addition. Accordingly, the value of the inhibition zone for those without prebiotic addition (13.18±7.403) was significantly lower than that of cutoff values of 20 with a significant difference of -6.820 (t= -6.514, df 49, P=0.000). Moreover, the inhibition effect of prebiotics (inulin and starch) against S. typhi at 37 °C for 24 h in part dish glucose as control, only the mean of inulin was found to be significantly lower than that of the cutoff value of 18 with the mean difference of -3.900 (t=-4.115, df 49, P=0.000). Other prebiotics of glucose and starch in 24 h showed negative inhibition. Probiotics are live microorganisms that have beneficial host effects by enhancing microbial balance in the intestine, whereas prebiotics are indigestible food components having beneficial effects by enhancing the activity and growth of one or more colonic bacteria. Lactobacillus filtrates had considerable effects against the test S. typhi isolates.