Soil salinity is a major abiotic stress that limits plant growth and productivity. Understanding the mechanisms of plant salinity tolerance can facilitate engineering for quality improvement. Apocynum venetum L. exhibits tolerance to salinity. Due to the lack of a genomic database, RNA-seq based transcriptomics and isobaric tag for relative and absolute quantitation (iTRAQ) based proteomic profiles of Apocyni Veneti Folium (AVF) exposed to four levels of salt treatments were performed. A total of 143, 162 and 167 differentially expressed proteins (DEPs) were found between salt-treated AVF compared with control, respectively. They were mainly involved in carbohydrate and energy metabolism, biosynthesis of metabolites and signal transduction. Furthermore, results showed that carbon and nitrogen metabolisms were altered under salt stress; low and moderate levels of salt stress enhanced photosynthetic functions and ramped up carbohydrate metabolism. However, severe salt stress depressed biosynthesis of secondary metabolites, consistent with the metabolomics results. In conclusion, the protein profiles combined with transcriptomics and metabolomics indicate that halophyte uses a multipronged approach to overcome salt stress, and provides some novel information for revealing the mechanisms of adaption and quality formation of this herbal medicine.