Previous studies have suggested that the presence of white-spot lesion is very probable when adjacent surface is affected by cavitated lesions. This study evaluated the potential of different fluoride-releasing restorative materials in arresting enamel white-spot lesions in approximal surface in contact with them, in vitro (I) and in situ (II). White-spot lesions were formed in 240 primary enamel specimens via pH-cycling. They were put in contact with cylindrical blocks of 6 materials (í µí±› = 20): composite resin, 2 high-viscous glass ionomer cements (HVGIC), resin-modified GIC, resin-modified nanoionomer, and polyacid-modified resin. In both studies I and II, these settings were designed to simulate the contact point between the restoration and simulated approximal lesion. For study I, they were subjected to a new pH-cycling cariogenic challenge for 7 or 14 days (í µí±› = 10). For study II, a randomized double-blind in situ design was conducted in two phases (7/14 days) to promote cariogenic challenge. At the end of both studies, specimens were collected for mineral analysis by cross-sectional microhardness. Higher mineral loss was observed for lesions in contact with resin (í µí± < 0.001). HVGICs were the most efficient in preventing mineral loss, whereas other materials presented an intermediate behavior. It is concluded that fluoride-releasing materials can moderately reduce white-spot lesions progression, and HVGIC can arrest enamel lesion in approximal surface in contact with them.