Helicases, motor proteins present in both prokaryotes and eukaryotes, play a direct role in various steps of RNA metabolism. Specifically, SF2 RNA helicases, a subset of the DEAD-box family, are essential players in plant developmental processes and responses to biotic and abiotic stresses. Despite this, information on this family in the physic nut (Jatropha curcas L.) remains limited, spanning from structural patterns to stress responses. We identified 79 genes encoding DEAD-box RNA helicases (JcDHX) in the J. curcas genome. These genes were further categorized into three subfamilies: DEAD (42 genes), DEAH (30 genes), and DExH/D (seven genes). Characterization of the encoded proteins revealed a remarkable diversity, with observed patterns in domains, motifs, and exon–intron structures suggesting that the DEAH and DExH/D subfamilies in J. curcas likely contribute to the overall versatility of the family. Three-dimensional modeling of the candidates showed characteristic hallmarks, highlighting the expected functional performance of these enzymes. The promoter regions of the JcDHX genes revealed potential cis-elements such as Dof-type, BBR-BPC, and AP2-ERF, indicating their potential involvement in the response to abiotic stresses. Analysis of RNA-Seq data from the roots of physic nut accessions exposed to 150 mM of NaCl for 3 h showed most of the JcDHX candidates repressed. The protein–protein interaction network indicated that JcDHX proteins occupy central positions, connecting events associated with RNA metabolism. Quantitative PCR analysis validated the expression of nine DEAD-box RNA helicase transcripts, showing significant associations with key components of the stress response, including RNA turnover, ribosome biogenesis, DNA repair, clathrin-mediated vesicular transport, phosphatidyl 3,5-inositol synthesis, and mitochondrial translation. Furthermore, the induced expression of one transcript (JcDHX44) was confirmed, suggesting that it is a potential candidate for future functional analyses to better understand its role in salinity stress tolerance. This study represents the first global report on the DEAD-box family of RNA helicases in physic nuts and displays structural characteristics compatible with their functions, likely serving as a critical component of the plant’s response pathways.