Objective To explore the effect of tranexamic acid combined with large-spot low-energy Nd:YAG laser on melasma area improvement in patients with stable melasma. Methods A total of 86 patients with stable melasma who received treatment in the Department of Medical Cosmetology, Huai'an Maternal and Child Health Care Center from December 2022 to March 2025 were selected as the research subjects, and they were divided into the control group and the study group by the envelope method, with 43 patients in each group. The control group was treated with tranexamic acid, and the study group was treated with tranexamic acid combined with large-spot low-energy Nd:YAG laser. The treatment effect, hormone levels, Erythema Index (EI), Melanin Index (MI) and melasma area improvement were compared between the two groups. Results The total effective rate of the study group (97.67%) was higher than that of the control group (83.72%) (P <0.05). The levels of MSH and SP in the study group after treatment were lower than those in the control group (P <0.05). The EI and MI of the study group after treatment were lower than those of the control group (P <0.05). The melasma area improvement of the study group after treatment was better than that of the control group (P <0.05). Conclusion Tranexamic acid combined with large-spot low-energy Nd:YAG laser has a synergistic effect in the treatment of melasma. This combined therapy can effectively reduce systemic hormone levels in patients, decrease the Erythema Index and Melanin Index, and reduce the area of melasma.