The mangrove plant Kandelia candel is a type of woody halophyte that grows in tropical and subtropical ocean intertidal zones and exhibits a high salt tolerance. In this study, 61,970 unigenes were obtained from the roots of 60-day-old K. candel seedlings treated with 0 (control), 200, 400, and 600 mM NaCl for 3 days with an N50 of 1510 bp. Moreover, 454, 311, and 2663 genes were differentially expressed under 200, 400, and 600 mM NaCl treatments, respectively. These differentially expressed genes were primarily involved in plant hormone signal transduction, carbohydrate and energy metabolism, amino acid metabolism, stress response, and defense. The levels of 12 important differentially expressed genes were confirmed by qRT-PCR, showing that the changing trend was generally consistent with the results of the transcriptomic analysis. In addition, physiological parameters involved in energy metabolism, amino acid metabolism, and the reactive oxygen species scavenging process were significantly increased under salt stress treatment, and the trend was consistent with the results of transcription and qRT-PCR. This study indicated that K. candel roots could tolerate high salt stress by enhancing ethylene signal transduction, maintaining a stable energy supply, increasing antioxidant capacity. Specially, we found that accumulation of γ-aminobutyric acid and glutamate, but not proline, might play an important role in salt tolerance in the roots of K. candel.