Objective: To investigate the effect of 1064-nm Q-switched Nd: YAG laser combined with tranexamic acid (TXA), glutathione (GSH), and vitamin C (VC) in the treatment of chloasma and its effects on serum luteinizing hormone (LH) and estradiol (E2) levels. Methods: Sixty patients diagnosed with chloasma were enrolled. Among them, 30 patients (Group A) were treated with a 1064-nm Q-switched Nd: YAG laser, while another 30 patients (Group B) were treated with the same laser equipment combined with TXA, GSH, and VC. They were compared in terms of their baseline data and the chloasma area and chloasma color score before and after treatment. Changes in the LH and E2 levels before and after treatment in the two groups were determined by using an enzyme-linked immunosorbent assay (ELISA). Skin lesion subsidence was compared between the two groups before and after treatment using the modified Melasma Area and Severity Index (mMASI) score. The efficacy, adverse reactions, and recurrence after treatment were compared. Results: After treatment, group B showed significantly lower parameters than group A, including the chloasma area and chloasma color, serum LH and E2 levels, mMASI scores and the recurrence rate (All P < 0.05). Group B exhibited a significantly higher effective rate than Group A. There were no statistically significant differences between the two groups in xerosis cutis or pigmentation (P < 0.05). Conclusion: 1064-nm Q-switched Nd: YAG laser combined with TXA, GSH, and VC can enhance the therapeutic effect on patients with chloasma, improve their chloasma area, chloasma color score, and skin lesion subsidence, and ensure the safety of treatment, as well as regulate their endocrine hormone levels, so it is worthy of clinical popularization.