Abstract Granitoids with evolved chemical signatures, intruding both oceanic crustal rocks and mantle peridotite, are well known in the Samail supra-subduction ophiolite of Oman and United Arab Emirates. The former are metaluminous tonalites and trondhjemites have positive εNd, relatively low δ18O values, resemble ridge ‘tholeiitic’ granitoids with MORB-like affinity, and formed by fractionation of basalt/gabbro or anatexis of oceanic crust. In contrast, the mantle-hosted granitoids are peraluminous, with negative εNd and high δ18O values. They can be modeled as having formed by mixing between partial melts of metabasalt and metasedimentary rocks with minimal mantle contribution. The mantle-hosted granitoids resemble typical peraluminous S-type granitoids (e.g. Himalaya, Variscan, Lachlan) but are compositionally distinct in having notably scattered data values of K2O, Na2O, CaO, Rb/Sr, relatively higher silica and, lower (Al2O3 + FeO + MgO + TiO2 wt%) and Th/Yb as compared to typical S-types. The mantle-hosted granitoids mainly originate from the subducted slab, and mostly intruded mantle peridotite in the lithospheric mantle, with no apparent association with the overriding oceanic plate and little interaction (e.g. assimilation) with the mantle. While the specific controls on geochemical variations remain speculative, results from this study show that the Samail mantle-hosted S-type granitoids are compositionally distinct from classic S-type granitoids formed in orogenic belts. While global S-type granitoids may be mineralogically similar, the Samail mantle-hosted granitoids preserve different geochemical signatures, reflecting their formation in distinct tectonic setting, including the mantle.