Dimenhydinate, an antihistamine agent, is effective for treating motion sickness and has a value for both civil and military application. We searched PubMed, the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials, EMBASE, CINAHL, Web of Science, BIOSIS Preview for related literatures. In this paper we reviewed the retrieved literatures and discussed the safety and efficacy of dimenhydrinate in the treatment of motion sickness. It was showed that although the first choice for motion sickness was scopolamine, dimenhydrinate was, however, the first choice for nausea and vomiting, which is partly because it can reduce gastric motility during motion sickness-inducing stimuli. Therefore, dimenhydrinate might be the first choice for treating motion sickness combined with vomiting and nausea.