Poly(l-lactic acid) (PLLA) nanocomposites containing various loadings of organo-modified montmorillonite were prepared via twin screw extrusion and solution casting in order to investigate the effect of processing route on the structure and the thermal properties of the fabricated nanohybrid materials. X-ray diffraction (XRD) testing indicated that a better dispersion of the modified inorganic filler can be achieved by solution intercalation. The interlayer distance of the mineral, and thus the type and structure of the nanohybrid formed, was found to be affected by the polymer content only in the case of the nanocomposites produced by the solution casting method. Thermogravimetric analysis (TGA) revealed that the hybrids prepared by melt compounding displayed increased thermal stability. Differential scanning calorimetry (DSC) showed that the fabrication route influences the crystallization process of the polymer.