Introduction The diabetic macular edema (DME) is a relevant cause of visual impairment in diabetes. The current treatments are limited by high costs, risk of infections and damage to retinal cells. Randomized controlled studies (RCTs) have investigated oral traditional Chinese medicines (TCMs) for the treatment of DME. We aimed at determining the efficacy and safety of oral TCMs by systematically reviewing the full set of studies. Methods and analysis Published RCTs will be searched through 12 databases until October 1, 2022. Two investigators will conduct independent literature search, data extraction and assessment of quality. The risk of bias will be judged with the version 2 of the Cochrane risk-of-bias tool. The RevMan software will be utilized to analyze data. Dichotomous data will be assessed by using odds ratios and 95% confidence intervals (CIs). We will evaluate continuous data by using weighted mean differences and 95% CIs. We are going to assess heterogeneity by Cochran's Q test and the I2 statistics. We plan sensitivity analysis and subgroup analysis to identify sources of heterogeneity. Funnel plots, Egger's tests and Begg's tests will be also performed.