Various kinds of organo-modified clays were dispersed at different amounts in an epoxy matrix. After clay addition, the viscosity of the epoxy resin resulted still acceptable for a possible usage as matrices for fiber-reinforced composites. The formation of intercalated microstructures led to substantial improvements of the thermal (glass transition temperature) and mechanical (fracture toughness) properties of the epoxy matrix. E-glass fiber/matrix interfacial shear strength was evaluated by the single-fiber microdebonding method. The introduction of organo-modified clays led to the formation of a stronger fiber-matrix interface, with an increase of the interfacial shear strength of about 30%. Concurrently, the evaluation of the fiber/matrix contact angle revealed an improved wettability when organo-modified clays were added.