Peganum harmala L. (Harmel) is widely employed in traditional Algerian medicine for treating various ailments. This study assessed the immunomodulatory effects of two extracts from P. harmala seeds, with a focus on their impact on selected immune system organs in female mice. Female NMRI white mice, Mus musculus, were intraperitoneally administered MCE (20.72 mg/kg) and TAE (37.75 mg/kg) for 20 days. Phytochemical analysis using thin-layer chromatography confirmed the presence of diverse alkaloids in the methanolic crude extract. The treatment induced behavioral alterations, changes in body weight, and modifications in relative organ masses. Biochemical assays revealed significant elevations in AST and ALT levels, while hematological analysis showed increased WBC, NEU, and P-LCR levels, accompanied by reductions in MCV, MCH, PLT, and MPV. Histological examination identified no structural damage to organ architecture; however, an accumulation of immune cells was observed in the thymus and adrenal glands. Despite the known anti-inflammatory properties of P. harmala, this study highlights its potential to disrupt immune homeostasis, particularly through excessive neutrophil proliferation. These findings underscore the need for cautious use of P. harmala to mitigate adverse effects, especially in conditions associated with immune dysregulation.