Background <p>Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. However, its clinical efficacy is limited by poor solubility and bioavailability.</p> Objectives <p>This study aimed to: Select an appropriate co-former for ibuprofen using computational tools; synthesize and characterize an ibuprofen-salicylic acid co-crystal and evaluate its solubility and dissolution properties.</p> Methods <p>Computational tools, including Avogadro, AutoDock Vina, and MGL Tools, were used for molecular docking, employing the Lamarckian genetic algorithm to determine docking scores to search for the selection of a co-former. Salicylic acid showed the best interaction and was selected. Four different methods were used to make ibuprofen-salicylic acid co-crystals. The co-crystal was analyzed using X-ray diffraction (XRD), thermal analysis, and spectroscopic techniques to confirm its structure. The aqueous solubility and dissolution rate of the co-crystal were evaluated and compared with pure ibuprofen.</p> Results <p>The ibuprofen-salicylic acid co-crystals synthesized using solvent-assisted co-crystallization technique exhibited a distinct crystalline structure and thermal behavior compared to their individual components. Aqueous solubility was significantly enhanced in comparison to pure ibuprofen.</p> Conclusion <p>The ibuprofen-salicylic acid co-crystal demonstrated improved aqueous solubility and dissolution rate, suggesting its potential for enhancing the oral bioavailability of ibuprofen.</p>