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.