Wheat (Triticum aestivum L.), a globally important staple crop, faces significant production challenges due to climate change, particularly drought stress.  Spirulina is known for its high nutritional value and potential biostimulant properties. Therefore, this study investigated Spirulina platensis extract (SpEx) potential to mitigate drought stress effects in wheat, integrating morphological measurements, gene expression data, and molecular docking. SpEx treatment significantly mitigated drought-induced reductions in plant height (18.2%), fresh weight (29.7%), and dry weight (15.7%). Gene expression analysis demonstrated upregulation of stress-responsive genes under SpEx treatment, with peroxidase showing the highest increase (6.13-fold) at 20 mg/ml SpEx concentration, followed by cytochrome P450 (5.23-fold), protein kinase (4.56-fold), and UDPGT (3.67-fold). GC-mass spectrometry analysis of SpEx revealed 27 bioactive compounds. Molecular docking studies of the SpEx-derived compounds with six key proteins (UDPGT, Cytochrome P450, Peroxidase, Protein kinase, ROS, and PCD) revealed varying binding affinities. Four compounds (Araguspongin, Lupeol, Silybin, and Strophanthidine) showed strong interactions with ROS and PCD proteins, exhibiting binding affinities superior to control ligands. ADMET analysis of these four compounds against ROS and PCD proteins demonstrated favorable pharmacological properties, with Araguspongin and Strophanthidine showing high GI absorption and all compounds complying with Lipinski's Rule of Five. Hierarchical cluster analysis of both morphological and gene expression data confirmed distinct grouping patterns between treated and untreated plants. These findings suggest that SpEx enhances wheat drought tolerance through multiple mechanisms, including improved morphological adaptations, enhanced stress-responsive gene expression, and molecular interactions with key stress-related proteins, offering promising applications for sustainable agriculture under water-limited conditions.