Non-steroidal Anti-Inflammatory Drugs (NSAIDs) are a group of often chemically unrelated compounds with some common therapeutic actions and side effects. However, the use of conventional NSAIDs has been restricted due to their side effects especially gastric erosion and ulcer so; the attention is focused on chalcones having gastric protectant and anti-inflammatory, activities by virtue of free radical scavengers. In the present study, alkoxy chalcones were synthesized by Claisen–Schmidt condensation reaction and evaluated for an antiulcer activity in the rats by indomethacin-induced gastric damage. The structures of the compounds were established by IR, 1H NMR and Mass spectral analysis. Possible correlation between observed biological activities and substituents at different positions on rings was also studied. The spectral analysis reveals that all the compounds 1a-1j was in good agreement with the standard values reported in the literature for these types of structures. Most of the synthesized compounds have shown good to moderate activity. Compounds with electron releasing groups (1i, 1j & 1g) at para position of both rings (R1 & R2) showed excellent antiulcer activity whereas compounds having pharmacophore such as iodo & bromo electron withdrawing groups (1b & 1h) at R2 position has mild action. The result obtained in the present study may be attributed to their antioxidant activity through scavenging of ROS, protection of glutathione peroxidase.