Purpose Measurement of macular pigment optical density (MPOD) can be conducted to assist in the diagnosis of multiple fundus diseases. Methods Fifty-four subjects with high myopia were prospectively recruited for a 3-month clinical trial. Detailed ophthalmologic examinations and MPOD measurements were performed. The subjects in each high myopia category group were randomly subdivided into 5 intervention groups, including a low-dose Lycium barbarum group (10 g Lycium barbarum, containing 10 mg of zeaxanthin and 1 mg of lutein), low-dose control group (1 mg of lutein), high-dose Lycium barbarum group (20 g of Lycium barbarum, containing 20 mg of zeaxanthin and 2 mg lutein), high-dose control group (2 mg of lutein), and a blank control group. Differences in the MPODs among the high myopia groups were calculated with Welch two-sample t tests. A linear mixed-effects model was constructed and Pearson's correlation analysis was performed to determine correlations between MPOD and other factors. The MPOD values at baseline and the 3-month follow-up were compared with the Mann-Whitney test. Results The category 1 group had a significantly higher MPOD than the category 2 (P = 0.02) and category 3 groups (P < 0.001). The category 2 group had a significantly higher MPOD than the category 3 group (P < 0.001). The MPOD significantly decreased with increasing axial length (AL) and decreasing best-corrected visual acuity (BCVA) in the category 1-3 groups and with increasing age and increasing intraocular pressure (IOP) in the category 2-3 groups. The MPOD was significantly higher in the group who received high-dose zeaxanthin from Lycium barbarum than in the group who received high-dose lutein at 3 months (P = 0.0403), while no significant difference was identified between the low-dose zeaxanthin group and low-dose lutein group (P = 0.1117). Conclusions The MPOD was negatively correlated with the category of high myopia. Supplementation of zeaxanthin from Lycium barbarum is beneficial in preventing the loss of macular pigment of high myopia patients.