Curcumin, a traditional Chinese and Indian treatment for many diseases, has recently been found to alter the in vitro infection processes of various viruses, including hepatitis C virus, human immunodeficiency virus, coxsackievirus, and Japanese encephalitis virus. The present study evaluated the cellular effects of curcumin in an in vitro (cellular) infection model of dengue virus. Within a dose range of 10 to 30 μM and a treatment period of 24 hours, the cytotoxicity of curcumin was low, as determined by MTT assays. Cells infected with dengue virus type 2 at a multiplicity of infection of 5 were treated with various concentrations of curcumin or the proteasome inhibitor MG132. Plaque assays, immunofluorescence analysis, western blots, and in-cell western assays were then performed. Treatment with 10, 15, and 20 μM curcumin decreased the number of plaques produced, caused an intracellular accumulation of viral proteins, and increased the level of Lys48 ubiquitin-conjugated proteins. At 20 μM curcumin, changes in cell and nuclear morphology and alterations in the actin cytoskeleton were also observed. Treatment with MG132 also reduced plaque production. These results show that curcumin can interfere with the infection processes of dengue virus and that this interference may not occur through direct effects on viral particle production but may result from curcumin's effects on various cellular systems such as the cytoskeleton, the ubiquitin-proteasome system, or the apoptosis process.