Insects coordinate a variety of mechanisms to overcome the feeding challenges, including gene transcriptional plasticity and stable symbioses in the gut. Here, Spodoptera frugiperda larvae were reared on corn and rice plants for successive generations to obtain two specific strains. The rice strain displayed a longer developmental period, lower female fecundity, and intrinsic growth rate at G1 and G5 but not at G10. KEGG analysis of the G1, G5, and G11 gut transcriptome indicated that detoxification enzymes might play vital roles in host adaptation. RNAi-mediated knockdown of CYP12A2 and UGT41B8, which were highly expressed in the gut of the rice strain, significantly reduced the larval adaptability to rice. Besides, the dsCYP12A2-treated larvae displayed an increased sensitivity to luteolin, a flavonoid phytochemical. The KEGG function prediction of gut microbiota indicated that the high enrichment level of metabolism in the rice strain would play essential roles in rice adaptation.