In the present project, a molecular imprinted polymer (MIP) was synthesized by using oxycodone (as the molecular template as well as the guest drug). The precipitation polymerization approach was used for preparation of the nano‐composites. Methacrylic acid (MAA), ethylene glycol dimethacrylate (EGDMA), and 2,2‐azobisissobutyronitrile (AIBN), were used as the functional monomer, the crosslinker, and as the photoinitiator, respectively. Moreover, to decrease the release rate of the drug, the bacterial cellulose (BC) was used in formulation of MIP contained‐transdermal patch. The release study of the drug by high performance liquid chromatography (HPLC) system (fitted with the Higuchi expression) has indicated that the MIP‐BC is a good candidate for the controlled transdermal drug delivery systems (TDDS). Finally, both the MIP‐, and the non‐molecular imprinted polymers (NIP)‐drug systems were designed and studied by the density functional theory (DFT) quantum chemical method, to investigate the potential energy surface (PES), structural properties, and adsorption behavior in the molecular view. The results showed that the formation of MIP‐oxycodone (−12.85 kcal mol−1) system is more favorable than the formation of the NIP‐oxycodone one (−11.35 kcal mol−1) (due to more hydrogen bonds, and polar interactions).