It has been proposed that the oceanic crust-mantle boundary may partly form through interactions between melts and the shallow mantle. Although this process may have a key role in defining the chemical signature of the oceanic crust, the effect of such melt-mantle interactions on the isotopic composition of the reacting melts has rarely been investigated. Here we report Re-Os isotopes and platinum group element (PGE) compositions of residual mantle harzburgites (olivine forsterite, Fo91–90) and troctolites (olivine Fo89–87) likely produced by melt-rock reactions at the Central Indian Ridge crust-mantle boundary. Although the harzburgites have high Os (4000–2500 pg/g) and unradiogenic isotopic signatures (187Os/188Os = 0.128–0.124), the troctolites show variable Os (383–16 pg/g) and highly fractionated 187Os/188Os ratios (0.129–0.140), which correlate with mineral (e.g., olivine Fo) and bulk-rock (e.g., CaO, Ni, and Cu) compositions. We relate this isotopic variability to the melt-mantle interaction process by which the troctolites generated. In particular, we suggest that the radiogenic Os signature was produced by selective assimilation of radiogenic interstitial sulfides from the reacted mantle. This mechanism is able to mimic the isotope variability of erupted melts, sustaining the idea that the crust-mantle boundary can act as a reactive filter for the melts extracted from the source region.