The effects of three medicinal plants in the feeds of juvenile Nile tilapia (Oreochromis niloticus) were investigated on growth, survival, immunity, and digestive histology at various inclusion levels: (A) Guiera senegalensis at 0, 1, 2, 4, and 8%; (B) Pluchea odorata at 0, 0.5, 1, 2, and 4%; (C) Piliostigma reticulatum at 0, 1, and 2%; and (D) a mixture of the three at 0, 1, and 2%. After 28 days of feeding, fish were infected with Aeromonas hydrophila for 12 days. The results showed that, except for G. senegalensis, the inclusion of the medicinal plants, alone or combined, enhanced the immune response. The diet with 4% P. odorata significantly increased plasma lysozyme and bactericidal activities without affecting feed conversion efficiency or growth. Despite improved immunity, none of the treatments enhanced post-infection survival rates. However, fish fed the 1% mixture showed healthier livers and intestines, with reduced cell swelling and normal lipid deposits, followed by the 2% mixture and the control. These results highlight the potential benefits of incorporating P. odorata and the plant mixture into the diets of Nile tilapia juveniles for enhancing their immune response against A. hydrophila.