The effects of methanol extract of Peganum harmala L. seeds were evaluated against Tribolium castaneum (Herbst). Larval growth was inhibited and food intake reduced when the extract was incorporated into the diet at concentrations of 2.5, 5 and 10%. All doses caused an increase in the duration of larval period and completely inhibited F1 progeny production. The main body metabolites were determined in last-instar larvae after feeding for 8 days on the diet treated with different doses. Protein and lipid contents were decreased with concentrations >2.5%. Glycogen content was reduced at a concentration of 10%. Tribolium castaneum larvae possessed two major and one minor α-amylase isoforms as determined by gel assays. Larvae fed the treated diet presented less activity of the major isoforms, while activity of the minor isoform was totally inhibited. The activity of this enzyme is not inhibited in vitro by seed extracts. Histological studies showed that P. harmala extracts caused a severe cytotoxicity on the epithelial cells of the midgut resulting in marked vacuolization of the cytoplasm and a large intercellular space. These findings suggest that seed extracts of P. harmala exert their toxic effect by severely damaging the midgut epithelial cells. This naturally occurring plant extract could be useful for control of T. castaneum.