Le Grand was a Franciscan Recollect friar in Douai, France. He was sent on the English mission to Oxfordshire where his Latin works on Descartes were translated into English. He had disputes with John Sergeant (1623–1707) and Samuel Parker (1640–88). His major work is An Entire Body of Philosophy According to the Principles of the Famous Renate des Cartes (1694). It was very popular and went through many editions.

Le Grand presents the cogito and the innate ideas of God, mind, and body, plus the eternal truths as the foundations of all knowledge. Descartes’ mechanism explains all bodily interactions and rules out the occult powers of Aristotelian matter. But even though Cartesians have certain knowledge of first principles and eternal truths, the application of these principles and truths to the material world is hypotheticodeductive, and the results are only probable. Thus, experimentation is important in Cartesian physics. A great deal of An Entire Body of Philosophy is devoted to detailed explanations of natural phenomena. Later, expositions of Newton often followed Le Grand's plan.

Le Grand provides a Cartesian ontology of things and modes to replace Aristotelian categories, but he keeps one substantial form, the Cartesian mind. All bodily properties derive from quantity, figure, and motion, and all action and passion in bodies are reducible to motion. The Aristotelian notion that there is nothing in the intellect that was not first in the senses is absurd according to Le Grand because we have innate, general ideas of God, mind, and body.

Le Grand's Entire Body of Philosophy was extremely popular in England, and the third book on The Want of Sense and Knowledge in Brute Animals was a topic of inexhaustible parlor conversation and theological debate in the late seventeenth century. Le Grand undertook to show in great detail how all animal behavior is mechanically generated by bodily interactions in the material world. With respect to bodily interactions generally, Le Grand was a thoroughgoing occasionalist (and reads Descartes as one too) and presents several arguments for God as the true source of causal interaction between bodies (see cause).