Gastrointestinal nematode (GIN) infections have negative impacts on animal health, welfare and production. Information from molecular studies can highlight the underlying genetic mechanisms that enhance host resistance to GIN. However, such information often lacks for traditionally managed indigenous livestock. Here, we analysed 600 K single nucleotide polymorphism genotypes of GIN infected and non-infected traditionally managed autochthonous Tunisian sheep grazing communal natural pastures. Population structure analysis did not find genetic differentiation that is consistent with infection status. However, by contrasting the infected versus non-infected cohorts using ROH, LR-GWAS, FST and XP-EHH, we identified 35 candidate regions that overlapped between at least two methods. Nineteen regions harboured QTLs for parasite resistance, immune capacity and disease susceptibility and, ten regions harboured QTLs for production (growth) and meat and carcass (fatness and anatomy) traits. The analysis also revealed candidate regions spanning genes enhancing innate immune defence (SLC22A4, SLC22A5, IL-4, IL-13), intestinal wound healing/repair (IL-4, VIL1, CXCR1, CXCR2) and GIN expulsion (IL-4, IL-13). Our results suggest that traditionally managed indigenous sheep have evolved multiple strategies that evoke and enhance GIN resistance and developmental stability. They confirm the importance of obtaining information from indigenous sheep to investigate genomic regions of functional significance in understanding the architecture of GIN resistance.