The intercalation of drug molecules with montmorillonit (MMT) using Acyclovir (ACV) as the model drug was focused on. The optimum conditions were studied based on orthogonal design, such as intercalation time and temperature. The intercalation composites were characterized by X-ray diffraction (XRD), Fourier transformed infrared (FT-IR), and thermogravimetric analysis (TGA). The experimental results reveal that ACV is successfully intercalated into the interlayers of MMT. The in vitro release experiments reveal that ACV is released from MMT steadily and pH dependent