Self-medication is one of the basic problems in the health system of Iran. The purpose of the present study is to determine the effect of theory-based education on the promotion of preventive behavior among mothers, concerning the self-medication for children. This study is an educational randomized controlled trial research that was designed and implemented for the first time in Iran. The samples consisted of 112 mothers with children under age six who referred to health centers of AzadShahr (a city in the north of Iran) from July 2015 to March 2016. They were selected through convenience sampling and then were randomly assigned to the intervention and control groups. Data collection instrument was a researcher-made questionnaire. Then educational program was performed for the intervention group through four educational sessions. After three months, data collection was repeated for the two groups and the data were analyzed using the SPSS-20 software with inferential statistics (independent t-test, paired t-test, and chi-square). The findings showed that based on T-test, after the educational program, the mean score ± standard deviation (SD) of knowledge between the intervention and control groups was 66.07 ± 16.58 and 70.45 ± 15.33, respectively (P = 0.149). Moreover, the mean score ± SD of performance was 86.88 ± 14.84 and 93.81 ± 10.36, respectively that there was a significant difference (P = 0.005). Three months after the educational program, based on the chi-square test, the prevalence of self-medication between intervention and control groups was 8.92% and 21.42%, respectively that there was a significant difference (P = 0.02). The educational interventions based on the theory of planned behavior reduced self-medication for children. Therefore, due to the high cost of drug production and the side effects of self-medication, especially in vulnerable periods such as in childhood, it is recommended that educational programs, based on this model, should be carried out in other health care centers in order to provide children health.