Daily chlorhexidine mouthwash is often recommended for preventing chemotherapy-induced oral mucositis. Povidone-iodine, NaCl 0.9%, water salt soda solution and chamomile mouthwash are also recommended. However, the effectiveness of these mouthwashes is unclear. Therefore, we performed a systematic review to assess the effectiveness of mouthwashes in preventing and ameliorating chemotherapy-induced oral mucositis. Based on study quality, three out of five randomized controlled trials were included in a meta-analysis. The results failed to detect any beneficial effects of chlorhexidine as compared with sterile water, or NaCl 0.9%. Patients complained about negative side-effects of chlorhexidine, including teeth discoloration and alteration of taste in two of the five studies on chlorhexidine. The severity of oral mucositis was shown to be reduced by 30% using a povidone-iodine mouthwash as compared with sterile water in a single randomized controlled trial. These results do not support the use of chlorhexidine mouthwash to prevent oral mucositis.