Background and aims: Utilization of diverse anti-acid materials is necessary for the preparation of compound omeprazole capsules. However, to gain the satisfied anti-acid effect, use of large amount of anti-acids is always difficult to swallow. This study aimed to develop a lightweight compound omeprazole capsule which could achieve immediately drug releasing with high anti-acid ability in stomach. Methods: Omeprazole was encapsulated in β-cyclodextrin to improve the drug solubility and stability. The influence of different factors on the efficiency of the drug encapsulation was investigated. In addition, the omeprazole inclusions were assessed by Fourier transform-infrared spectroscopy, differential scanning calorimeter, and X-ray diffraction. Finally, anti-acids materials such as magnesium oxide (MgO) and sodium bicarbonate (NaHCO 3) were used to reduce the weight of the capsule contents. Results: Compared to the market omeprazole capsule (ENCHENG ®), the omeprazole compound capsule demonstrated significantly improved drug dissolution (the maximum release ratio was 95.42 ± 2.51%) in simulated gastric environment. Moreover, rabbit pharmacokinetics showed that the area under the plasma concentration-time curve (AUC 0-t) was significantly increased to 54180.11 ± 6483.16 min•ng•mL-1 (p < 0.05), compared with that (39011.55 ± 6637.08 min•ng•mL-1) of the currently used capsules (EN-CHENG ®). Conclusions: The light compound omeprazole capsule could be an effective and swallowable oral delivering system for Acid-Related Disorders.