This study assessed the sensitivity of S. typhi to extracts of commonly used plants in treatment of typhoid in Ogbomoso, Oyo State, Nigeria. Ethnobotanical survey was conducted using a structured questionnaire. Powdered leaves of plants were extracted by maceration in distilled water. In vitro sensitivity of S. typhi to the extracts were assessed using agar well diffusion method. Groups of rats were infected orally with 0.5 McFarland suspension of S. typhi. Bacteremia in the animals was monitored by plating on Salmonella-Shigellar agar. Biochemical parameters were determined spectrophotometrically. Histological analysis was performed using H&E staining method.  S. typhi was sensitive only to P. guajava and A. indica leaf extracts. V. amygladina (90.31%) and C. papaya (92.26%) showed highest percentage inhibition of S. typhi comparable with ciprofloxacin (99.86%). Haematological parameters varied significantly (p<0.05) among the groups. Antioxidant status of rats, total protein, albumin and the corresponding globulin level increased significantly (p<0.05) in the groups treated with P. guajava and A. indica. C. papaya and C. citratus ameliorated the histopathological damages observed in the liver and intestine of S. typhi infected rats. The studied plants have direct activities against S. typhi, thus reflecting the reason for their combination in traditional system of medicine.