Background The main purpose is to investigate the effect of LiCO3 as an add-on therapy with radioactive iodine in increasing the cure and decreasing the T4 level compared to radioactive iodine alone. The primary outcome is the cure rate as defined by the number of hyperthyroid patients who became euthyroid or hypothyroid. The secondary outcome is the T4 level. Methods Four databases were searched (PubMed, Scopus, Web of Science, and Cochrane central library). The inclusion criteria were randomized and non-randomized clinical trials of hyperthyroidism patients receiving LiCO3 with radioiodine compared with hyperthyroidism patients receiving radioactive iodine alone. Included studies were appraised with the risk of bias version 2 tool, according to the Cochrane Handbook for Systematic Reviews of Interventions 5.1.0. Results Nine studies were eligible for inclusion in the study, six randomized control trials and three non-randomized control trials. There were 477 patients in the intervention group and 451 patients in the control group. The cure rate was not significantly different between the two groups, while it was significantly increased with 5000 to 6500 mg optimized cumulative dose of LiCO3 compared with the control group, P = 0.0001. The T4 level showed no significant difference between the two groups, P = 0.13. Conclusions LiCO3 adjunct to radioactive iodine did not show significant differences compared with radioactive iodine alone in terms of cure rate or decreasing T4 level. However, the dose of 5000 to 6000 mg of LiCO3 may increase the cure rate.