He soon became involved with the Coterie Holbachique, a group of radical French Enlightenment thinkers centered around the Paris salon of Baron d'Holbach. Priding himself on a through knowledge of the classics, Naigeon would also edit a French translation of the works of Seneca begun by Nicolas La Grange, publishing it along with Diderot's Essai sur les régnes de Claude et de Néron (Paris, 1778). Other editorial work included the Essays of Montaigne, and a translation of Toland’s philosophical letters
Naigeon became the editor, compiler, and commentator of Diderot's works after the latter made him his literary executor.
He published an incomplete edition of Diderot's works in 1798 after writing Mémoires historiques et philosophiques sur la vie et les ouvrages de Diderot, an unfinished commentary on his life and works. Naigeon's only original stand-alone work was Le militaire philosophe, ou Difficultés sur la religion, proposées au Pére Malebranche (London and Amsterdam, 1768) which was based on an earlier anonymous manuscript, and whose final chapter was written by d'Holbach. Naigeon continued his attacks on religion in his Dictionary of Ancient and Modern Philosophy in the Encyclopédie méthodique (1791–1794).
In his address to the National Assembly in 1790 (Adresse à l'Assemblée nationale sur la liberté des opinions) he called for absolute freedom of the press, asking the Assembly to withhold the name of God and religion from their declaration of the rights of man.