Algae-driven processes, such as direct CO2 fixation into glycerol, provide new routes for sustainable chemical production in synergy with greenhouse gas mitigation. The marine microalgae Dunaliella tertiolecta is reported to accumulate high amounts of intracellular glycerol upon exposure to high salt concentrations. We have conducted a comprehensive, time-resolved systems biology study to decipher the metabolic response of D. tertiolecta up to 24 h under continuous light conditions. Initially, due to a lack of reference sequences required for MS/MS-based protein identification, a high-quality draft genome of D. tertiolecta was generated. Subsequently, a database was designed by combining the genome with transcriptome data obtained before and after salt stress. This database allowed for detection of differentially expressed proteins and identification of phosphorylated proteins, which are involved in the short- and long-term adaptation to salt stress, respectively. Specifically, in the rapid salt adaptation response, proteins linked to the Ca2+ signaling pathway and ion channel proteins were significantly increased. While phosphorylation is key in maintaining ion homeostasis during the rapid adaptation to salt stress, phosphofructokinase is required for long-term adaption. Lacking β-carotene, synthesis under salt stress conditions might be substituted by the redox-sensitive protein CP12. Furthermore, salt stress induces upregulation of Calvin–Benson cycle-related proteins.