The aim was to investigate the enamel health benefits of a novel toothpaste with active tetracalcium phosphate/monetite mixtures under de/remineralization cycling. The enamel de/remineralization cycling protocol was consisted of demineralization in 1% aqueous solution of citric acid at pH 3.6 with following treatment with toothpastes and soaking in remineralization storage solution. Effectiveness of toothpastes to promote remineralization was evaluated by surface microhardness measurements, enamel erosion depth, analysis of surface roughness and fluorescent optical method. The novel tetracalcium phosphate/monetite toothpaste had the same remineralization potential as commercial calcium silicate/phosphate toothpaste and significantly higher than control storage solution group (p<0.05). Surface roughness was significantly lower after addition of fluorides to dentifrice (p<0.05). The enamel erosion depth was significantly reduced by applying toothpastes as compared to negative control (p<0.05) and did not differ from calcium silicate/phosphate toothpaste (p>0.66). The results showed that dentifrice formulations containing active tetracalcium phosphate/monetite mixture with or without fluoride addition had excellent enamel remineralization potential under de/remineralization cycling and successfully promote remineralization of enamel with daily using in the form of toothpaste.