The paper focuses on the weathering processes affecting gneissic rocks of the western Sila Grande Massif (Calabria, Italy) through the development of an interdisciplinary research based on field studies and investigations, minero-petrographical analyses and geochemical modeling. Both physical and chemical weathering affect gneissic rocks of the study area, where the combination of tectonic and past climatic conditions played an important key role in the development of complex and deep weathering profiles. Field surveys and cut slope analyses highlight articulated and complex geometric relationships between various classes of weathering (i.e., out-of-sequence weathering horizons giving rise to a partial, or even complete inversion of the “normal” weathering profile). The weathering profile has turned out particularly intense, as classes IV, V and VI are widespread. Among the class VI, the colluvial soils are prominent in comparison whit the residual soils. Borehole logs, that confirm the intensity and complexity of weathering profiles in deep, allow to estimate the presence of weathered rocks to be at least 70 m in thicknesses.The main mineralogical modifications linked to weathering processes concern the partial transformation of biotite and the partial destruction of feldspars (mainly plagioclases), associated with the neoformation of secondary mineralogical phases (clay minerals and Fe-oxides). Neoformed clay minerals (such as sericite, illite and mixed layer phases) and ferruginous products replaced feldspars and biotite during the most advanced weathering stage. Results of XRD analyses and geochemical modelling provide a good indication on the secondary mineral assemblage due to the increase of the weathering intensity (form class III to class VI) that reflects the different contributions of chemical elements provided by dissolution of silicate minerals into the surrounding groundwater system. The chemical composition of the studied rock samples and the oxides variations suggest a removal of some alkali (Na and K) and alkaline earth (Ca and Mg) into solution as a consequence of weathering reactions. The chemical analysis and the weathering indices (CIA, PIA, CIW and CIW’) show a marked alteration process, with ferromagnesian minerals and feldspars probably dissolved and leached into the surrounding groundwater system. The CO2-controlled dissolution of plagioclase appears to be the most important reaction during chemical weathering. The progressive dissolution results then dominated by biotite, followed by a minor amounts K-feldspar, chlorite and garnet; whereas the sillimanite shows a neglectable amounts. The secondary solid phases observed during the geochemical modeling (illite, followed by vermiculite, ferrihydrite and saponite) are similar to those found in this natural system. The proposed approach could be used to characterize weathered crystalline rocks and related weathering profiles in similar geological setting, and the obtained results represent a key point for the evaluation of the control exerted by weathering on landscape evolution under current environmental settings in terms of sediment generation, soil erosion rates, and mass movements, and for the mechanical characterization of weathering profiles for engineering geological purposes.