Oral mucositis frequently occurs in patients undergoing chemoradiotherapy. Oral care and cryotherapy are recommended for its prevention. Rebamipide mouthwash is clinically used as a hospital-compounded formulation because of its reactive oxygen species scavenging activity. However, patient-reported palatability and acceptability of this formulation remain unclear. This study aimed to assess the palatability and acceptability of rebamipide mouthwash in patients with head and neck cancer. The analysis included 43 patients newly prescribed this formulation (91% received cisplatin-based chemoradiotherapy). At initial use, palatability and overall acceptability were evaluated using 5-point scales, and taste attributes using a 100-mm visual analog scale (VAS). Three weeks later, patients completed a questionnaire regarding adherence and perceived need for formulation improvement. Receiver operating characteristic (ROC) curve analysis determined the bitterness VAS cut-off score for predicting favorable palatability and acceptability. Based on this cut-off, outcomes were compared between groups. Favorable ratings for palatability and acceptability were reported by 42% of patients. The median bitterness VAS score immediately after use was 34.0, the highest among all attributes, and persisted 5 min after use. ROC curve analysis identified a bitterness VAS cut-off of 29. Compared with the low-VAS group (<29), the high-VAS group showed significantly lower proportions of favorable ratings and a significantly higher perceived need for formulation improvement. Adherence to prescribed use did not differ significantly between groups. These findings suggest persistent bitterness may reduce the palatability and acceptability of rebamipide mouthwash in these patients. Improving formulation taste, particularly addressing persistent bitterness, may enhance acceptability and support consistent use.