Rotavirus (RV) infections cause severe life threatening diarrhea in young children and immunocompromised individuals. Several effective vaccines have been developed for young children but are not protective against all strains of RV, and there are no anti-RV therapeutics. Our laboratory has discovered a decrease in the number of infectious simian RV particles (SA114f) in human intestinal cell line, HT29.f8 cells with the addition of either of two stilbenoids, arachidin-1 (A1) or arachidin-3 (A3). This suggests effects on the host cell and RV replication. We examined the cellular effects of human RV strain (Wa) on a human intestinal cell line (HT29.f8) and an African green monkey kidney cell line (MA104) treated with/without either arachidin. Both cell lines demonstrated apoptotic characteristics that were modulated with the addition of either A1 or A3, and the size and population of the released virus particles were significantly altered. Likewise, the number of infectious virus particles released from the arachidin treated cells were significantly reduced. This data supports the RV therapeutic potential of A1 and A3.