Donnolo is the earliest Jewish writer on medicine, and one of the few Jewish scholars of South Italy at this early time. What remains of his medical work, Sefer ha-Yaḳar (Precious Book), was published by Steinschneider in 1867, from MS. 37, Plut. 88, in the Medicean Library at Florence, and contains an "antidotarium," or book of practical directions for preparing medicinal roots. Donnolo's medical science is based upon Greco-Latin sources; only one Arabic plant-name occurs. He cites Asaph.
In addition, he wrote a commentary to the Sefer Yeẓirah, dealing almost wholly with astrology, and called Ḥakemani (in one manuscript, Taḥkemoni; see II Sam. xxiii.8; I Chron. xi.11). At the end of the preface is a table giving the position of the heavenly bodies in Elul 946. The treatise published by A. Neubauer (Rev. Et. Juives, xxii.214) is part of a religio-astrological commentary on Gen. i.26 (written in 982), which probably formed a sort of introduction to the Ḥakemani, in which the idea that man is a microcosm is worked out. Parts of this introduction are found word for word in the anonymous Orḥot Ẓaddiḳim (or Sefer Middot) and the Shebeṭ Musar of Elijah Kohen. It was published separately by Jellinek (Der Mensch als Ebenbild Gottes, Leipzig, 1845).
The style of Donnolo is worthy of note; many Hebrew forms and words are here found for the first time. He uses the acrostic freely, giving his own name not only in the poetic mosaic of passages from the Book of Proverbs in the Bodleian fragment, but also in the rimed prose introduction to the Ḥakemani. He is also the first to cite the Midrash Tehillim. In the Pseudo-Saadia commentary to Yeẓirah there are many citations from Donnolo, notably from a lost commentary of his on the Baraita of Samuel. A. Epstein has shown that extensive extracts from Donnolo are also to be found in Eleazar Roḳeaḥ's Yeẓirah commentary (ed. Przemysl, 1889), even to the extent of the tables and illustrations. He is also mentioned by Rashi (to Er. 56a), by Samuel of Acco (who calls the Ḥakemani the Sefer ha-Mazzalot), and by Solomon ben Judah (1424) in his Ḥesheḳ Sheiomoh to Judah Ha-Levi's Cuzari.