Highly necessary to evaluate the effectiveness of preventive interventions to prioritize them at the community level. We aimed to systematically investigate the related studies on the effects of fluoride varnish and fissure sealant on dental caries in 6-12 children. We searched PubMed, EMBASE, Web of Science, Cochrane Library and Scopus databases using Fluoride Varnish, Fissure Sealant, Caries, and Oral Health keywords. The timeframe selected to search for articles is from 2000 to Dec 2020. CMA software: 2 (Comprehensive Meta-Analysis) was used to perform the meta-analysis. The intervention groups in this study were fluoride varnish and fissure sealants, each of them compared to the control groups. We included nine studies. In the intervention group 84,380 and control group 11,254 individuals were studied. Eight of the studies were Randomized Clinical Trial (RCT) and Field RCT, and two was non-RCT. In the overall Fluoride Varnish efficacy study, 4 were fully effective, 1 was ineffective, and all 4 were completely effective for Fissure Sealant. There was a significant difference between decayed, missing, and filled permanent teeth (DMFT) and decayed, missing, and filled primary teeth (dmft) indices in both interventions and comparison groups. Moreover, the mean difference of DMFT for Fluoride Varnish and Fissure Sealant in the intervention and control groups were -0.55 and -0.29, respectively (P=0.00). Due to the efficacy of fissure sealant and fluoride varnish in preventing dental caries in children aged 6-12 yr, these interventions can be considered as health priorities of societies and health systems interventions in countries.