Amoebiasis is caused by Entamoeba histolytica infection. In African countries amoebiasis is endemic and one of the top 10 causative agents of diarrhea in children. The common diagnostic method for Entamoeba spp. in Egypt is microscopic observation and identification of cysts/trophozoites in fecal samples. It is known that metronidazole (MTZ) is the choice of treatment for amoebiasis. However, drug resistance and side effects are considered to be disadvantages. In this study children and adolescents infected with E. histolytica complex (Eco) have been divided into two groups. As a control treatment, one group received MTZ capsules. The other group (intervention) received herbal medicinal capsules of Nigella sativa (N. sativa) powder to test for its effectiveness against Eco infection and compare its results with the control group. Socio-demographic data, cure rate, recession of symptoms and residual side effects of treatment were evaluated for the patients. In the intervention group, N. sativa showed a cure rate of 78.8% compared to 91.2% in MTZ- control group with no significant difference. Eco infected patients complained about diarrhea, bloody stool and abdominal pain with significant reduction in N. sativa- control group symptoms (from 93.9 to 15.2 %) compared to MTZ. Treatment with MTZ caused several symptomatic residual side effects of metallic taste, anorexia, abdominal pain and diarrhea. After N. sativa treatment, however, no residual symptoms were noted, an indicator of its safety. N. sativa was safe, cost-effective, herb with potential promising effectiveness against Eco infection.