Insects' salivary glands and their secretions play a pivotal role in their adaptation to host plants. Hyphantria cunea, a significant pest of both agriculture and forestry, feeds on a variety of host plants, yet the specific functions of its salivary glands in this adaptation process remain largely unclear. In this study, we compared the adaptability of fifth-instar larvae to Populus davidiana × P. bolleana (PDB) and artificial diet (AD). Through transcriptome analysis, 1439 differentially expressed genes (DEGs) were identified in the salivary glands of fifth-instar larvae feeding on PDB and AD. These DEGs include genes encoding various digestive and detoxification enzymes, which are enriched in pathways related to salivary secretion, digestion, and drug metabolism. Compared to larvae fed AD, the majority of digestive and detoxification enzyme genes were upregulated following consumption of PDB. Furthermore, the larvae enhanced the activities of two digestive enzymes (α-amylase and lipase) and four detoxification enzymes (cytochrome P450 monooxygenase, carboxylesterase, glutathione-S-transferase, and UDP-glycosyltransferases) in their salivary glands, thereby digesting the nutrients in the leaves while detoxifying the secondary metabolites contained within them. Silencing of CYP9E2 significantly reduced larval food intake and weight gain, and prolonged larval developmental duration. Taken together, our study identifies the salivary glands of H. cunea larvae as a critical tissue for executing digestive and detoxification functions, enhances understanding of the larval adaptability to host plants via salivary glands, and provides valuable insights for managing H. cunea infestations.