In this study, ampicillin drug loaded with alginate and nanocellulose film was prepared by solution casting method. Nanocellulose and ampicillin incorporated into alginate to improve both mechanical and swelling properties. Interaction of ampicillin with alginate and nanocellulose was proved by ATR-FTIR spectra. The formulated ampicillin loaded Alg/NC film gave acceptable physicochemical properties compared with Alg-amp film and was able to deliver the drug in a prolonged release pattern. In vitro drug release showed that alginate could provide an immediate release of ampicillin with further enhanced nanocellulose, and followed by a sustained release over 500 min of the remaining drug. The present study exhibited a simple and useful approach to systematically design for providing drug release profiles.