Lansopraole (LNS) is one of the most frequently used anti-ulcer drug, but its poor aqueous solubility, low bioavailability, and instability limits its clinical application. In this study, glycyrrhizin (GLY), a natural complexing agent obtained from licorice was used to deliver lansoprazole (LNS) for the treatment of ulcer. LNS/GLY complexes with and without magnesium oxide (MgO) as an alkalizer were prepared using spray drying method in order to improve the release and stability of LNS, and examine its anti-ulcer effects on rats. Among three developed complexes (F1-F3), F3 complex (LNS/GLY (1:1.5 w/w, with MgO) was optimized with highest process yield (85.7 ± 2.3%) and drug content (91 ± 4.3%). The optimized spray-dried complex (F3) was further evaluated for DSC, FTIR, PXRD, SEM, photostability and in-vitro release studies. An enhanced drug release and improved photo-protection was confirmed by NMR studies. Further in-vivo anti-ulcer studies showed a significant alleviated macroscopic and microscopic stomach damage and reduction in hemorrhagic lesions and ulcer index.