The fall armyworm (FAW) Spodoptera frugiperda is a destructive and polyphagous pest of many essential food crops including maize and rice. The FAW is hard to manage, control, or eradicate, due to its polyphagous nature and voracity of feeding. Here, we report the characterization and functional analysis of the detoxification gene CYP302A1 and how S. frugieprda larvae use a detoxification mechanism to adapt host plants. Results demonstrated that CYP302A1 expression levels were much higher in midgut tissue and the older S. frugiperda larvae. Our current studies revealed the enhanced P450 activity in the midguts of S. frugiperda larvae after exposure to rice plants as compared to corn plants and an artificial diet. Furthermore, higher mortality was observed in PBO treated larvae followed by the exposure of rice plants as compared to the corn plant. The dsRNA-fed larvae showed downregulation of CYP302A1 gene in the midgut. At the same time, higher mortality, reduced larval weight and shorter developmental time was observed in the dsRNA-fed larvae followed by the exposure of rice plant as compared to the corn plant and DEPC-water treated plants as a control. These results concluded that the inducible P450 enzyme system and related genes could provide herbivores with an ecological opportunity to adapt to diverse host plants by utilizing secondary compounds present in their host plants.