Herbal products have been used in aquafeed as a dietary supplement. In the current study, the immunomodulatory efficacy of nonfermented (MO) and/or fermented (FMO) Moringa oleifera combined leaf and seed mixture as feed additives for Nile tilapia, Oreochromis niloticus, was evaluated in terms of phagocytic capacity, spleen immune-related cytokines, immunoglobulin M (IgM) gene expression, as well as nitric oxide production, after a 30-day feeding trial. To conduct the experiment, a total of 180 O. niloticus fingerlings were randomly divided into five groups (36 fish each, in triplicate); the control (1st group) which fed on a basal diet, 2nd group and 3 rd group were fed on MO 5% and MO 10%, 4th group and 5 th group were fed on FMO 5% and FMO 10%. The results demonstrated that MO10%-supplemented diets significantly (P < 0.005) reduced immune cells' phagocytic capacity, serum nitrite level, immune-related cytokines (IL-1β, TNF-α, IL-10), and IgM gene expression. Meanwhile, those fed on FMO10%, FMO5%, and MO5%-supplemented diets exhibited a significant (P < 0.05) improvement in the same tested parameters, with the greatest effects on FMO 10%. In conclusion, dietary supplementation with FMO especially at 10% level increased nonspecific and humoral immune parameters, and the outcome of this study recommends that FMO is a promising immune-stimulatory feed-additive candidate for Nile tilapia.