The main objective of this study was determining the prevalence and antibiotics resistance pattern of Salmonella and Shigella sp. from diarrheal patients attending Nekemte Referral Hospital. A total of 422 patients were included in the study and their sociodemographic and clinical information was collected using questionnaire. Stool samples of the patients were collected and processed following standard bacteriological protocols. Presumptive colonies of Salmonella and Shigella species were identified and subcultured to their respective genera by standard biochemical tests. Antibiotics susceptibility of the isolates was tested using disk diffusion assay. The prevalences of Salmonella and Shigella sp. among the patients were 7.1% and 2.1%, respectively. The antimicrobial susceptibility test results of the isolates showed that they are highly resistant to amoxicillin (30 μg). In contrast, the isolates showed relatively lower resistance level to ceftriaxone (30 μg), nalidixic acid (30 μg), norfloxacin (10 μg), and ciprofloxacin (5 μg). This study revealed 9.2% prevalence of Salmonella and Shigella sp. which were resistant to commonly prescribed antibiotics. Thus, intervention measures such as health education, provision of safe drinking water, improvement of waste disposal systems, and surveillance of antibiotics susceptibility of the pathogens should be done regularly.