Calcium phosphate-based technologies show promising efficacy as adjunctive treatment for fluoride therapy in the management of early carious lesions. Apacider® Mangostin Adhesive Pastes (AMAP) have been introduced as new alternative for the prevention and management of initial lesions. This study aimed to examine the effects of fluoride varnish combined with AMAP on remineralization of artificial enamel carious lesions in comparison to fluoride varnish alone, and AMAP alone. Artificial carious lesions were created on the buccal surfaces of 60 extracted premolars. Specimens were randomly divided into 5 groups: (1) fluoride varnish application at first day in combination with AMAP once a day continuously for 10 days, (2) fluoride varnish application at first day only, (3) AMAP application once a day continuously for 10 days, (4) blank AMAP application once a day continuously for 10 days, and (5) no treatment. All samples were treated under pH cycling for 10 days. Remineralization effect was evaluated by the difference in surface microhardness before and after agent application. There was a significant change in the mean surface microhardness before and after application in all groups (p < 0.001 each). A significant decrease in microhardness was observed in the fluoride varnish combined with AMAP group and fluoride varnish alone group, while a significant increase was found in AMAP alone group. The extent of the change was statistically different between AMAP groupand fluoride varnish combined with AMAP group (p < 0.001). Comparison between fluoride varnish combined with AMAP group and fluoride varnish group showed no statistical difference (p = 0.99). In conclusion, AMAP has highest remineralization potential on artificial carious enamel lesions among all comparison groups. The application of fluoride varnish in combination with AMAP had no remineralization effect on artificial enamel carious lesions.