The objective of this study is to conduct a systematic review of the literatures on the effect of treatment combining 9300 nm carbon dioxide (CO2) lasers and fluoride on prevention of enamel caries. A literature search was performed using PubMed, Scopus, and Web of Science. The keywords were ((9300 nm) OR (9.3 µm) OR (carbon dioxide laser) OR (carbon dioxide lasers) OR (CO2 laser) OR (CO2 lasers)) AND ((fluoride) OR (fluorides)) AND ((dental caries) OR (caries) OR (remineralization) OR (remineralization) OR (demineralization) OR (demineralization)). Meta-analysis was performed to compare the change in mineral content by laser irradiation and fluoride treatment (F + L) with that of fluoride treatment (F) and laser treatment (L). The search identified 946 potential publications and five laboratory studies using a chemical model for cariogenic challenge and determining mineral loss of the enamel were included in this review. Meta-analysis comparing F + L with L on enamel showed a standard mean difference of −1.58 (CI: −2.13, −1.03). Meta-analysis comparing F + L with F on enamel showed a standard mean difference of −1.84 (CI: −2.30, −1.39), with low heterogeneity (I2 = 49%, p = 0.04). In conclusion, F + L was better than L and F in preventing enamel demineralization.