This study aimed to compare the ability of casein-phosphopeptide amorphous-calcium-phosphate (CPP-ACP) and glass-ionomer (GI) in remineralizing proximal artificial caries lesions (ACLs). Molar enamel-slabs were divided into: original-lesion control, intra-oral controls, and experimental (CPP-ACP or GI) groups. Specimens received ACLs and were bonded on subject maxillary first molars. After 4-weeks, mineral density (MD) was analyzed by μCT. Compared to control, CPP-ACP increased MD at 0-38/68-84 microns and the GI group had an increase at 0-68 microns, with a greater increase in MD compared to the CPP-ACP group from 0-53 microns. The mean percent remineralization (%R) showed differences between the GI, CPP-ACP groups and their paired controls. GI tended to increase remineralization more than CPP-ACP. In conclusion, CPP-ACP and GI demonstrated distinct remineralizing ability. GI induced greater remineralization in the superficial lesion, while CPP-ACP remineralized the lesion body. Their effects on percent remineralization and reducing lesion depth of proximal ACLs were similar.