Objective To investigate the clinical effect of laser combined with tranexamic acid, glutathione and vitamin C in the treatment of chloasma. Methods A total of 78 patients with chloasma admitted to our hospital from February 2022 to January 2023 were selected as the research objects. According to the random number table method, they were divided into control group and observation group, with 39 patients in each group. The control group was treated with tranexamic acid, glutathione and vitamin C, and the observation group was treated with laser combined with tranexamic acid, glutathione and vitamin C. The clinical efficacy, chloasma area, chloasma color score and serum index were compared between the two groups. Results The total effective rate of treatment in the observation group was 94.87%, which was higher than 76.92% in the control group (P <0.05). After treatment, the chloasma area and chloasma color score in the observation group were lower than those in the control group (P <0.05). After treatment, the levels of E2 and MDA in the observation group were lower than those in the control group, and the level of SOD was higher than that in the control group (P <0.05). Conclusion Laser combined with tranexamic acid, glutathione and vitamin C is effective in the treatment of patients with chloasma, which can effectively reduce the area of chloasma and reduce the color of chloasma. At the same time, it can effectively control the levels of E2 and MDA, optimize the oxidative stress response, and promote the recovery of skin lesions.