Salinity stress is a significant environmental factor limiting the productivity of Jatropha curcas, a biofuel crop of economic importance. Understanding the molecular mechanisms behind salinity tolerance in J. curcas is crucial for improving its resilience. This study aimed to analyse the differential proteomic profiles of two J. curcas genotypes under salt stress to identify candidate proteins that could serve as molecular targets for salinity response. The treatments comprised two genotypes of J. curcas (CNPAE183—tolerant, CNPAE218—sensitive) and two NaCl concentrations (0- and 150-mM L−1). After protein extraction, purification, and quantification, we detected 114 differentially accumulated proteins (DAPs). Of these DAPs, 42 (65%) and 23 (35%) were identified as either exclusive or overexpressed in CNPAE183, while 36 (72%) and 14 (28%) were exclusive to or overexpressed in CNPAE218 when compared to the two genotypes under the same 150 mM L−1 NaCl exposure. Protein ontology analysis revealed that CNPAE183 exhibited higher expression of proteins related to photosynthesis and branched-chain amino acids, whereas CNPAE218 showed upregulation of proteins involved in cellular respiration and stress response. A heatmap generated through principal component analysis further distinguished the proteomic responses of the two genotypes under salt stress. These findings highlight the molecular basis of salt tolerance in J. curcas, offering potential applications in breeding programs to enhance crop resilience. The identification of key proteins may also contribute to environmental sustainability by improving salt tolerance in biofuel crops under saline conditions.