The postmortem interval (PMI) is difficult to estimate in later stages of decomposition. There is therefore a need to develop reliable methodologies to estimate late PMI. This study aims to assess whether there is a correlation between changes in the mineral composition of human teeth and the estimation of PMI. X-ray diffraction (XRD) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy techniques were performed to address this challenge. Forty healthy human teeth obtained from odontological clinics were stored at different times (0, 10, 25, 50 years; N = 10/group). XRD and ATR-FTIR parameters related to the structure and composition of teeth were studied. Our results showed that the crystallinity index, crystal size index, mineral-to-organic matrix ratio (M/M) and carbonate/phosphate ratio (C/P) had the strongest association with PMI. For larger PMIs, there was a significant increase in crystallinity, crystal size and M/M ratio, while the C/P ratio showed a specific decrease with increasing PMI. According to our results, the parameters of crystallinity, crystal size, M/M ratio and C/P ratio can be considered highly accurate in determining a PMI of 10 years of data; crystallinity and mineral maturity can be considered useful in determining a PMI of 25 years; and crystallinity and mineral maturity can be considered highly accurate in determining a PMI of 50 years. A particular XRD index was identified as the most suitable parameter to estimate PMI: crystallinity. The joint use of XRD and ATR-FTIR analyses could be a promising alternative for dating human teeth.