Peptic ulcer (PU) is a condition that is commonly linked to prolonged non-steroidal anti-inflammatory drugs (NSAIDs) use. This study aimed to examine the possible gastroprotective outcome of dapagliflozin (DAPA) on indomethacin (INDO)-provoked PU. Three rat groups were utilized, group I (control); group II (PU group) administered single oral dose (50 mg/kg) of INDO on the 14^th day; group III (treatment group) administered daily oral dose (3 mg/kg) of DAPA for 14 days and PU was induced by INDO on the last day. The gastric mucosa was examined microscopically. Moreover, malonaldehyde (MDA), glutathione reductase (GSH), tumor necrosis factor-alpha (TNF-ɑ), nuclear factor kappa B (NF-κB), interleukin 10 (IL-10), cyclooxygenase-II (COX-II), prostaglandin E2 (PGE2) and pepsin levels were assessed using ELISA. Our findings revealed that PU group displayed a significant rise in MDA, TNF-ɑ, NF-κB and pepsin levels. Pre-treatment with DAPA attenuated these changes. Also, PU group exhibited reduced GSH, IL-10, COX-II and PGE2 levels which was reversed in the DAPA group. Microscopically, ulcerated and hemorrhagic areas were revealed in the INDO group which was mitigated by DAPA. In conclusion, DAPA showed gastroprotective effects against INDO-induced ulcerated rats through its anti-oxidant, anti-inflammatory actions and mucosal protective effect by increasing PGE2 and reducing pepsin levels.