Diclofenac sodium (DS), one of the most used non-steroidal anti-inflammatory drugs worldwide, is often detected in wastewater and natural water. This drug is ecotoxic, even at low concentrations. Therefore, it is essential to fabricate low-cost adsorbents that can easily and effectively remove DS from contaminated water bodies. In this study, a polyethyleneimine (PEI)-modified magnetic cellulose nanocrystal (MCNC) was prepared with a silane coupling agent as a bridge. TEM, FTIR, XRD, and VSM were used to demonstrate the successful preparation of MCNC-PEI. This composite adsorbent exhibited efficient DS removal. Furthermore, the adsorption performance of MCNC-PEI on DS was optimal under mildly acidic conditions (pH = 4.5). Adsorption kinetics showed that the adsorption process involves mainly electrostatic interactions. Moreover, the maximum adsorption capacity reached 299.93 mg/g at 25 °C, and the adsorption capacity only decreased by 9.9% after being reused five times. Considering its low cost, low toxicity, and high DS removal capacity, MCNC-PEI could be a promising adsorbent for treating DS-contaminated water.