Introduction: As all the topical fluorides contain a high concentration of fluorides and it is started at an early age when the swallowing reflexes are not well established, there is every chance the child may ingest a high amount of fluoride. As there are inconsistencies related to the usage of fluoride varnish in children, there is a need to study the toxicological aspects of fluoride varnish. Objectives: The objectives of this study were to estimate the amount of fluoride output through urine after the application of fluoride varnish and gel and to assess the safety levels of the same in early childhood caries (ECC) patients. Methodology: This study was conducted on twenty ECC-rehabilitated children of age group 4–6 years who were divided into two phases. In Phase I, the children were subjected to acidulated phosphate fluoride (APF) gel, and in Phase II, they were subjected to Fluor Protector varnish. In Phase I, the urine samples of each child were collected for the estimation of fluoride level which was considered as the baseline sample. After the application of APF gel, two urine samples were collected at 24 and 48 h for the estimation of fluoride levels. The same children were included in Phase II and were given placebo dentifrice for 7 days before commencing the procedure. The same experiment was repeated after the application of Fluor Protector varnish, and the collected urine samples were subjected for the estimation of fluoride level in laboratory with the use of fluoride ion-specific electrode and a miniature calomel reference electrode coupled to potentiometer. Values were recorded and the urinary fluoride concentration at different time intervals in each group was compared using the Friedman test followed by the Wilcoxon signed-rank test. Results: The mean urinary fluoride concentration in Group 1 at 24 h was 1.09 (standard deviation [SD] = 0.52) and at 48 h 0.74 (SD = 0.44). The mean urinary fluoride concentration in Group 2 at 24 h was 1.18 (SD = 0.65) and at 48 h 0.94 (SD = 0.59). There was a gradual increase in the 24th-h sample of both the groups, which also showed a decline of fluoride concentration at the 48th h. When both the groups were compared, Group 2 showed a marginal increase in fluoride concentration at different intervals of time, which was statistically nonsignificant. Conclusions: Fluor Protector varnish had an increased sustained release of fluoride ions when compared to APF gel, and there was a gradual decrease in the fluoride concentration which suggested that the fluoride concentration was approximating the baseline level (the safety level). The present study has provided a sound basis of recommendation for the safe and effective use of professionally applied fluoride products.