Background: Haemonchus contortus is a blood-feeding gastrointestinal nematode (GIN) that parasitizes in the abomasum of ruminants. Infections caused by this nematode possess a serious threat to livestock production worldwide. The influence of medicinal plants using for control of haemonchosis on the local immune response of abomasal mucosae in GIN-infected sheep, however, has not been reported. This study evaluated the effect of Artemisia absinthium and Malva sylvestris as dietary supplements containing bioactive compounds on antioxidant response and histopathological changes in the abomasa of the lambs. Twenty-four lambs were divided into four groups: unsupplemented lambs (UNS), lambs supplemented with A. absinthium (ART), lambs supplemented with M. sylvestris (MAL), and lambs supplemented with both plants (ARTMAL). All lambs were infected orally with approximately 5000 L3 larvae of H. contortus. The experiment was conducted for 75 d, all animals were then slaughtered, and the abomasal tissues were examined for antioxidant parameters and histopathology.Results: Methanolic extracts of wormwood and mallow were separated into four fractions by semi-preparative high-performance liquid chromatography, which identified saccharides, phenols, phenolic acids, flavonoids, polyphenols, esters, fatty acids, lipids, and other substances. The concentration of malondialdehyde in the abomasal mucosa was lower in ARTMAL (P < 0.05), and the total antioxidant capacity was higher in MAL (P < 0.05), than in UNS. Serum antioxidant parameters were not affected by the treatments (P > 0.05). Histopathological changes were mainly detected in the mucosal membrane of the abomasum, with the presence of infiltrates of inflammatory cells in MAL, ART, and ARTMAL. Increase mucus production was observed in the ARTMAL. The number of mast cells was significantly higher in UNS and ART than MAL (P < 0.01 and P < 0.05). Plasma cell numbers were higher in ARTMAL than MAL (P < 0.05). Abomasal tissue regenerated more frequently in ARTMAL than the other experimental groups.Conclusions: These results represent the first report of the impact of A. absinthium and M. sylvestris on antioxidant parameters and local immune responses of abomasal mucosa of lambs infected with a GIN parasite. Wormwood and mallow applied as dietary supplements may increase the resistance of lambs to GIN infections.