Beta-nicotinamide adenine dinucleotide (NAD⁺) is a ubiquitous electron carrier involved in many metabolic pathways. In the greenhouse, NAD⁺ was confirmed for its potential to reduce disease severity of powdery mildew (Podosphaera xanthii) on squash and halo blight (Pseudomonas syringae pv. phaseolicola) on snapbean. However, the underlying molecular mechanisms in these crops following NAD⁺ treatment remain unknown. RNA-seq has been developed to investigate a variety of biological responses by measuring the abundance of different RNAs. In this study, we monitored the change of genes in plants after NAD⁺ treatment by RNA-seq. True leaves of both crops were collected 4 h after NAD⁺ or water (mock) treatment. Total RNA was extracted and subjected to RNA-seq assays. Preliminary data analysis revealed that 15344 and 7552 genes were upregulated, and 8479 and 12502 genes were downregulated in squash and snap bean, respectively. These results indicate that exogenous NAD⁺ induces profound transcriptome changes in both crops. Meanwhile, 25 and 13 lectin receptor kinase (LecRK) genes, which are homologous to the Arabidopsis extracellular NAD⁺ (eNAD⁺) receptor gene LecRK-I.8, were upregulated in squash and snap bean, respectively. These results suggest that squash and snap bean may also use LecRKs to sense eNAD⁺. Further studies will focus on RNA-seq analysis of the kinetics of NAD⁺-induced transcriptome changes and identification of the eNAD⁺ receptors in squash and snap bean.