Background: Giardia intestinalis is a flagellate protozoan that infects both humans and animals. Formation of reactive oxygen species (ROS) during several physiological processes in tissues and cells is indicative of the pathogenesis of different parasitic infections involving Giardia lamblia. Objectives: the current study aimed to assess the potential effects ofPunica granatumon interactions of G. intestinalis with the intestinal barrier and its role in ameliorating oxidative stress in a murine model using serum biochemical analysis of both malondialdehyde (MDA) and reduced glutathione (GSH). Methodology: Five experimental groups were involved: Group I included control healthy, group II included infected untreated, group III included infected-treated with metronidazole, group IV included infected-treated with P. granatum, Group V received P. granatum for seven days before and also during induction of infection then regular administration of the drug for an additional seven days. Results: The highest serum levels of MDA (nmol/ml) were expressed in group II 7.03 ± 0.19 followed by group IV that was 5.29 ± 0.62 then group V 4.17 ± 0.28, while group III had 3.58 ± 0.18. On the other side, the highest serum levels of GSH (nmol/ml) were expressed in group V 9.93 ± 0.18, followed by group IV 7.41 ± 0.19nmol/ml, while in group III was 6.11 ± 0.40. Group II had 5.00 ± 0.15 nmol/ml. There was significant difference between different groups. Conclusions: Decreased expression of MDA in prophylactic and treated groups by P. granatum, moreover increased expression of GSH in group V prophylactic group explains the protective effect of P. granatum against lipid peroxidation and oxidative stress induced by Giardia infection.