The current study reported the potential activity of the aqueous extract of Moringa oleifera leaves in reducing granulomatosis induced by Schistosoma soluble egg antigen (SEA).Twenty-five healthy individuals and fifty Schistosoma mansoni/hepatitis C virus (HCV) co-infected patients were enrolled in the current study. The granulocytes were isolated and used to induce in vitro granuloma using SEA-conjugated polyacrylamide beads in the presence of interleukin (IL)-17 (125 pg/mL). After 3 days, the granuloma was treated with the aqueous extract of Moringa leaves(0.1 mg/mL). Praziquantel (PZQ, 0.1 mg/mL) was used as a reference drug. On the 7^th and 14^th days, the granuloma index (G.I) was determined and tumor necrosis factor (TNF)-α, H₂O₂, and nitric oxide (NO) levels were measured in the culture supernatant. The microscopic examination showed a significant reduction (P<0.05) in the granuloma size in response to PZQ or Moringa extract after 7 and 14 days, respectively, in the healthy subjects; the reduction induced by Moringa was significant comparing with PZQ after 14 days. A significant decrease was also recorded in the granulocytes' mediators as H₂O₂ (in both healthy subjects and co-infected patients) and NO (in healthy subjects only) in response to Moringa extract comparing with PZQ after 14 days. However, TNF-α showed a significant increase (only after 14 days) in the granuloma treated with PZQ or Moringa extractcompared with the untreated granuloma of healthy individuals. In conclusion, the Moringa extract showed a higher protective activity than PZQ in reducing granuloma, possibly due to affecting the production of granulocytes' mediators.