Objective To explore the clinical efficacy and cost-effectiveness of honey, low-temperature oxygen atomization and conventional mouthwash on chemotherapy-induced oral mucositis (CIOM) in patients with acute lymphoblastic leukemia (ALL). Methods 129 ALL patients who were hospitalized in the hematology department of a tertiary first-class hospital in Yinchuan City of Ningxia from February to May 2023 and met the inclusion and exclusion criteria were selected, they were randomly divided into honey group, low-temperature oxygen atomization group, and conventional mouthwash group, with 43 cases in each group. During chemotherapy period, the honey group applied honey to oral mucosa surface, the low-temperature oxygen atomization group inhaled granulocyte stimulating factors through low-temperature oxygen atomization, the conventional mouthwash group gargled with prescribed mouthwash. Results There were 7(16.28%), 9(20.93%), and 20(46.51%) patients with CIOM in honey group, low-temperature oxygen atomization group, and conventional mouthwash group, respectively. The incidence and severity of CIOM among three groups of patients were statistically different (H=11.598, P=0.003). Honey and low-temperature oxygen atomization were superior to conventional mouthwash in the prevention and treatment efficacy on CIOM in ALL patients (both P < 0.05), but the efficacy was no statistically different between honey and low-temperature oxygen atomization (P>0.05). The cost of honey group was lower than low-temperature oxygen atomization group and conventional mouthwash group (both P < 0.05), although the low-temperature oxygen atomization group has certain therapeutic effect, its cost was much higher than that of the honey group and the conventional mouthwash group(both P < 0.05). Conclusion Honey has a better prevention and treatment effect on CIOM in ALL patients, and can also reduce the hospitalization cost of patients.