Objective To explore the efficacy of laser transdermal administration of tranexamic acid combined with glycyrrhetinic acid glycoside in the treatment of chloasma. Methods A total of 90 patients with chloasma admitted to the plastic surgery and beauty department of our hospital from December 2021 to November 2022 were selected as the research objects. They were divided into experimental group A, experimental group B and control group by random number table method, with 30 cases in each group. The control group was given topical 3% tranexamic acid essence combined with oral compound glycyrrhizin tablets. The experimental group A was given Q-switched Nd:YAG laser-assisted topical 3% tranexamic acid essence on the basis of the control group. The experimental group B was given lattice laser-assisted subcutaneous topical 3% tranexamic acid essence on the basis of the control group. The clinical efficacy, melasma area and severity index (MASI) score, treatment satisfaction, skin stain change rate and adverse reactions were compared among the three groups. Results The total effective rate of treatment in the experimental group A was higher than that in the control group and the experimental group B (P <0.05). The MASI score of group A was lower than that of control group and group B (P <0.05). The change rate of skin color spot in group A was higher than that in control group and group B (P <0.05). The treatment satisfaction of experimental group A was higher than that of control group and experimental group B (P <0.05). No obvious adverse reactions occurred during the treatment of the three groups. Conclusion Q-switching Nd:YAG laser assisted topical administration of 3% tranexamic acid essence combined with oral glycyrrhizin is effective in the treatment of chloasma, which can effectively reduce the area of chloasma, reduce the severity of the disease, and the probability of pigmentation is small. Meanwhile, the patient's satisfaction with the treatment effect is high, there are no obvious adverse reactions, and the safety is high.