Objective To analyze the effect of Er:YAG erbium laser combined with semiconductor laser treatment on pigment clearance in patients with oral mucosal pigmentation. Methods A total of 54 patients with oral mucosal pigmentation admitted to the Department of Periodontology and Mucosa, Yinchuan Stomatological Hospital from January 2022 to June 2024 were selected, and they were divided into the reference group and the study group by the random number table method, with 27 patients in each group. The reference group received semiconductor laser treatment, and the study group received Er:YAG erbium laser combined with semiconductor laser treatment. The pigment clearance effect, oral mucosal health score, satisfaction rate and adverse reaction rate were compared between the two groups. Results The total effective rate of pigment clearance in the study group (88.89%) was higher than that in the reference group (74.07%) (P <0.05). The oral mucosal health score of the study group after treatment was (0.96±0.12)points, which was lower than (1.52±0.38)points of the reference group (P <0.05). The satisfaction rate of the study group (92.59%) was higher than that of the reference group (70.37%) (P <0.05). The incidence of adverse reactions in the study group (3.70%) was lower than that in the reference group (22.22%) (P <0.05). Conclusion Er:YAG erbium laser combined with semiconductor laser treatment has a good effect in patients with oral mucosal pigmentation. It can effectively improve the total effective rate of pigment clearance, help to enhance the health of oral mucosa, and has a low incidence of adverse reactions after treatment, with high patient satisfaction.