This work was carried out to assess the immunomodulatory activity of Moringa oleifera (M. oleifera) and Curcuma longa (C. longa) extracts in normal and cyclophosphamide (CP)-immunosuppressed rats. Different doses (200 and 400 mg/kg of body weight) of aqueous extracts of M. oleifera or C. longa were administered orally and daily to male albino rats for 15 days before intraperitoneally (i.p.) injection with saline or CP (30 mg/kg of body weight) for three consecutive days. Other rats received a mixture of aqueous extracts of M. oleifera (200 mg/kg of body weight) and C. longa (200 mg/kg of body weight) orally and daily for 15 days before i.p. injection with saline or CP for three consecutive days. Rats receiving distilled water orally and i.p. injected with saline were used as normal control animals. Rats receiving CP only were used as immunosuppressed control animals. Relative spleen weight, hematological parameters, serum concentrations of interleukin-10 (IL-10) and interferon-γ (IFN-γ) as well as spleen histopathological changes were determined on day 19. From the obtained results it could be concluded that the mixture of M. oleifera and C. longa restored the decrease in the relative spleen weight and modulated the hematological changes in immunosuppressed rats. Lowered levels of serum IFN-γ in CP-treated rats were found to be increased by administration of both extracts. At the same time the level of serum IL-10, which was elevated by CP, was reduced by administration of both extracts. The spleen histoarchitecture was severely damage by CP, while the aqueous extract-protected groups showed normal spleen architecture. The results indicate that extract of M. oleifera, C. longa and their mixture display considerable potential as an immunomodulator in CP-immunosuppressed male rats.