Gastrodia elata Blume (GEB) is a traditional herbal plant that has been used in Asian countries for centuries as an anticonvulsant, analgesic, and also as a sedative for treating general paralysis, epilepsy, vertigo, and tetanus. Although numerous reports have addressed the effects of GEB against degenerative diseases, no previous study has examined the possible gastroprotective effects of GEB. Here, we examined the effects of pretreatment with GEB (0.02 ml/g, p.o.) in a mouse water immersion restraint (WIR) stress-induced gastric lesion model. Our results revealed that mice pretreated with GEB had significantly fewer gastric lesions than their respective controls. Moreover, GEB-treated mice showed significant decreases in serum and gastric nitric oxide (NO) levels to 50 and 28%, respectively. To examine one possible mechanism underlying this effect, we used reverse transcription-polymerase chain reaction (RT-PCR) to examine NOS mRNA expression in gastric lesion tissues. Our results revealed that the mRNA expression of inducible nitric oxide synthase (iNOS) was reduced by approximately 50% in GEB-pretreated mice versus the controls, whereas the mRNA expression levels of endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) remained unchanged. These findings collectively suggest that GEB significantly protects the gastric mucosa against WIR-induced gastric damage, at least in part by decreasing NO levels via suppression of iNOS mRNA expression.