A combined Raman spectroscopy and electron probe microanalysis study of the heavily shocked Grove Mountains (GRV) 052049 meteorite revealed the largest chemical fractionation of natural ringwoodite, and composition-dependent variation of the intensities and/or wavenumbers of Raman bands. With Fa content [atomic ratio of Fe/(Fe+Mg)] of ringwoodite varying from 27.8 to 81.6 mol%, the peak position of the single band around 290 cm−1 (SB1), which relates to the SiO4 translation mode, shifts from 296.0 to 284.6 cm−1, and one of the doublets around 790 cm−1 (DB1), which relates to the symmetric stretching of SiO4, shifts from 796.3 to 782.7 cm−1. In addition, the relative intensities of SB1 and the other band of the doublet around 840 cm−1 (DB2), which relates to asymmetric stretching of SiO4, increases with Fa content. Based on the paired Raman-EPMA data, single-peak and two-peak calibrations were established, which can be used to derive Fa contents of ringwoodite from the Raman spectra. The accuracy of Raman-derived Fa content of ringwoodite is better than ±5 mol%. The correlation of SB1 intensity with the Fa content of ringwoodite suggests that the vibration of SB1 is enhanced with the substitution of Mg2+ by Fe2+. The correlation between Raman spectra and the chemical composition of ringwoodite have potential applications in on-line measurement of high-pressure experiments and in situ mineralogical determination in future planetary explorations.