Fluorine (F) and strontium (Sr) are key elements in the de-and remineralization of teeth. To quantitatively analyze the distribution of F and Sr, micro-particle-induced gamma/X-ray emission (PIGE/PIXE) technique was used. The cavities were prepared and filled with the fluoride-and Sr-containing restorative materials (FSCMs) in extracted human molars. The single-section enamel specimens were prepared by slicing from the buccal to lingual surface including the FSCMs. After 5 weeks of automatic pH cycling, the demineralization was calculated by integrated mineral loss (ΔIML) from transverse-microradiography. The distributions of F and Sr were analyzed by the PIGE/PIXE technique. The micro-PIGE/PIXE technique indicated a fluorine uptake difference between the enamel surface and enamel cavity wall. ΔIML of FSCMs were significantly lower than intact enamel. The micro-PIGE/PIXE technique enables measurement of F and Sr uptake from FSCMs into enamel, which would be beneficial for research on caries development and prevention.