The aim of this in vitro study was to evaluate the influence of treatment time on the remineralization performance of nanoencapsulated fluoride dentifrices on initial carious lesions. Ninety-six human enamel samples were allocated to eight groups (n = 12): 50% NanoF + 50% free NaF, 100% NanoF, 100% NaF (positive control), and placebo (negative control), using two different treatment times (one and five minutes) for each dentifrice tested. After the carious lesion induction, the specimens were submitted to a pH remineralizing cycling model for seven days. Surface microhardness was measured before and after carious lesion induction and after treatment. The percentage of surface remineralization was calculated for each study time. Data were analyzed using two-way ANOVA and ANOVA repeated-measures tests followed by the Bonferroni correction (p < 0.05). Remineralization differences were observed in the dentifrices analyzed according to the treatment time used. NanoF formulations with 50% (one-min treatment) and 100% (five-min treatment) promoted significant remineralization of enamel after the caries challenge when compared to the placebo dentifrice (p < 0.05). Thus, time was considered an important factor for the fluoride release system. Nanotechnology can be a promising system for caries remineralization as it makes fluoride available on the dental surface for a longer time.