Georg Friedrich Grotefend had a son, named Carl Ludwig Grotefend, who played a key role in the decipherment of the Indian Kharoshthi script on the coinage of the Indo-Greek kings, around the same time as James Prinsep, publishing Die unbekannte Schrift der Baktrischen Münzen ("The unknown script of the Bactrian coins") in 1836.

While there he published his work De pasigraphia sive scriptura universali (1799), which led to his appointment in 1803 as prorector of the gymnasium of Frankfurt, and shortly afterwards as conrector.

This medal made by the local engraver Heinrich Friedrich Brehmer links Grotefend's jubilee with the 500th anniversary of the school where he taught.

[3] Grotefend was best known during his lifetime as a Latin and Italian philologist, though the attention he paid to his own language is shown by his Anfangsgründe der deutschen Poesie, published in 1815, and his foundation of a society for investigating the German tongue in 1817.

In 1823/1824 he published his revised edition of Helfrich Bernhard Wenck's Latin grammar, in two volumes, followed by a smaller grammar for the use of schools in 1826; in 1835–1838 a systematic attempt to explain the fragmentary remains of the Umbrian dialect, entitled Rudimenta linguae Umbricae ex inscriptionibus antiquis enodata (in eight parts); and in 1839 a work of similar character upon Oscan (Rudimenta linguae Oscae).

Previously, in 1836, he had written a preface to Friedrich Wagenfeld's translation of the Sanchoniathon of Philo of Byblos, which was alleged to have been discovered in the preceding year in the Portuguese convent of Santa Maria de Merinhão.

The Old Persian cuneiform inscriptions of Persia had for some time been attracting attention in Europe; exact copies of them had been published by Jean Chardin in 1711,[4] the Dutch artist Cornelis de Bruijn and the German traveller Carsten Niebuhr, who lost his eyesight over the work; and Grotefend's friend, Tychsen of Rostock, believed that he had ascertained the characters in the column, now known to be Persian, to be alphabetic.

[9][8][11] His article appeared as an appendix in Heeren's book on historical research and was entitled "On the Interpretation of the Arrow-headed Characters, particularly of the Inscriptions at Persepolis".

In Persian history around the time period the inscriptions were expected to be made, there were only two instances where a ruler came to power without being a previous king's son.

[25][26] This time, academics took note, particularly Eugène Burnouf and Rasmus Christian Rask, who would expand on Grotefend's work and further advance the decipherment of cuneiforms.

[29] Building on Grotefend's insights, the task was performed by Eugène Burnouf, Christian Lassen and Sir Henry Rawlinson.