Due to practical difficulties in quantifying fluoride exposure in populations, practical and accurate biomarkers can play a major role in the surveillance of fluoride. Among different fluoride biomarkers, spot urine and nail-clippings have gained more attention due to their ease of acquisition. However, there is no robust consensus about the accuracy of these biomarkers for the estimation of fluoride exposure. This systematic review and meta-analysis aimed to synthesize evidence on the association between fluoride exposure and the fluoride concentration of spot urine and nail-clippings. This review was conducted and reported using the PRISMA Statement. Nine databases (Medline, CINAHL, Web of Science, Scopus, ScienceDirect, Sage Journals Online, Campbell Collaboration, Cochrane Collaboration, and Embase); search engines (Google and Google Scholar); and grey literature were searched up to September 2022. All screening, data extraction, and quality assessments were conducted in duplicate. All experimental and observational research studies that reported the correlation between fluoride exposure and fluoride concentrations of spot urine and/or nail clippings were included. The Mixed-Methods Appraisal tool was used to assess the methodological quality of the included studies. A random effect meta-analysis was carried out to determine the relationship between fluoride exposure and fluoride concentration of biomarkers (i.e., spot urine and nail clippings). Forty-four studies met the inclusion criteria. A total of 694,578 participants were included in this review. Twenty-five studies were included in the meta-analysis. The primary meta-analysis showed a moderate correlation of 0.674 (95%CI: 0.623-0.725, n=25) between fluoride intake and fluoride concentration of spot urine and a strong correlation of 0.938 (95%CI: 0.520-1.355, n=11) between fluoride intake and the fluoride concentration of nail-clippings in all age groups. The findings of secondary meta-analyses showed a strong positive correlation between fluoride intake and fluoride/creatinine ratio of spot urine in children (0.929; 95%CI: 0.502-0.991; n=2). In conclusion, spot urine and nail-clippings have the potential to be employed as non-invasively obtained biomarkers in populations. However, due to the scarcity of high-quality, relevant studies, more research is needed to establish the validity of these biomarkers.