Alhagi camelorum, a desert shrub known for its impressive drought tolerance, exhibits notable resilience under arid conditions. However, the underlying mechanisms driving its drought resistance remain largely unexplored. This study aims to investigate these mechanisms by exposing A. camelorum to osmotic stress using varying polyethylene glycol (PEG) concentrations (1%, 5%, 10%) in a controlled laboratory setting. Growth analysis revealed significant inhibition and phenotypic changes with increasing PEG levels. Transcriptomic analysis, including differentially expressed gene identification, GO enrichment analysis, and hierarchical cluster analysis of genes in roots and shoots, identified key pathways associated with drought adaptation, such as ABA-activated signaling, cell wall biogenesis, photosynthesis, and secondary metabolite biosynthesis. Notably, some genes involved in these pathways exhibited tissue-specific expression patterns and showed PEG concentration-dependent regulation. Key findings include the dose-dependent (R2 > 0.8) upregulation of a proline-rich protein (Asp01G030840) and a BURP domain-containing protein (Asp02G039780), as well as critical genes involved in cell wall biogenesis (encoding Pectinesterase inhibitor domain-containing and Fasciclin-like arabinogalactan protein), and secondary metabolite biosynthesis (encoding enzymes for terpenoid and flavonoid biosynthesis). The regulation of these genes is likely influenced by phytohormones such as ABA and other stress-related hormones, along with significant transcription factors like ABI4, TALE, MYB61, GRAS, and ERF. These insights lay the groundwork for further research into the functional roles of these genes, their regulatory networks, and their potential applications in enhancing drought resistance in desert plants and agricultural crops.