In the context of climate change and increasing aridification, Vachellia tortilis subsp. raddiana stands out for its remarkable ability to adapt to Morocco’s arid environments. It mobilizes physiological and biochemical mechanisms that strengthen its resilience to water stress. This study examines its responses to drought and highlights the potential of exploiting its bioactive compounds. Under severe water deficit, relative water content decreases from 62 ± 3% to 38 ± 2%, while proline increases from 0.8 ± 0.1 to 2.8 ± 0.3 µmol/g DM and soluble sugars rise from 12.3 ± 1.5 to 32.8 ± 2.1 mg/g DM, ensuring effective osmotic adjustment and the maintenance of cellular homeostasis. At the same time, chlorophyll a and b contents decrease by 46% and 30%, respectively, indicating an adaptive regulation of the photosynthetic apparatus. Beyond these physiological strategies, the leaves of Vachellia tortilis subsp. raddiana respond to environmental stresses through the remarkable accumulation of secondary metabolites, contributing both to defense and functional potential. They exhibit high concentrations of polyphenols (281 ± 1.2 mg GAE/g DM) and flavonoids (57.5 ± 0.9 mg QE/g DM), conferring notable antibacterial activity of leaf extracts against Escherichia coli (9 ± 1.1 to 12 ± 1.4 mm) and Staphylococcus aureus (12 ± 1.4 to 17 ± 1.3 mm). These findings highlight the dual value of the species: a model of physiological resilience and a promising resource for the sustainable development of crops adapted to arid regions under climate change.