Shigellosis causes severe diarrhea and, in some cases, death in children. In this study, we investigated the in vitro and in vivo anti‐shigellosis efficacy of some aqueous herbal extracts or their chosen mixtures, including fenugreek seed, black seed, clove, garlic, and ginger. The antibacterial potential was assessed by well diffusion and microdilution assays. The extracts' minimum inhibitory concentrations ranged from 0.39 to 12.5 mg/ml. The water extract of garlic and combinations of garlic with either fenugreek or clove extracts had the highest antibacterial efficacy, hence these extracts were chosen for the in vivo investigation. Rats were given a Shigella dysenteriae inoculum and then administrated two doses (100 and 200 mg/kg bw) of the selected herbal extracts or the antibiotic ciprofloxacin (20 mg/kg bw) to treat Shigellosis in vivo. The results showed that garlic and clove extract mixtures (G6, 200 mg/kg bw), garlic and fenugreek mixtures (G7 and G8, 100 and 200 mg/kg bw), and ciprofloxacin group (G9, 20 mg/kg bw) had the best anti‐Shigellosis efficacy. G7 (garlic and fenugreek mixtures (100 mg/kg bw) outperformed almost all other groups evaluated. This group had lower defecation frequency, lower stool‐Shigella loudness, restored body weight, recovered hematological, and liver and kidney functions, besides exhibited no anatomical alterations in the colon tissue that were comparable to the uninfected group. As a result, in the treatment of Shigella, this extract combination may be suggested as a viable therapeutic alternative to antibiotics.