Laguna returned to Spain in 1536, then travelled to England, lived some years in the Netherlands and collected herbal remedies in all the places he stayed to verify Dioscorides's prescriptions.

He was provided with accommodations in Venice by the Spanish ambassador Diego Hurtado de Mendoza, a preeminent humanist and proprietor of a nutritional library.

Laguna finally returned to Spain in 1557, after another extended stay in the Netherlands lasting three years; he served as doctor to Charles V and Philip II.

Laguna worked on literary, historical, philosophical, political (Europe the Self-Tormentor, that is to say, she miserably torments herself and laments her own disgrace) and medical subjects, as a typical homo universalis of the Renaissance.

Laguna still considered the theory of the four humors effective, but he showed scepticism with respect to alchemy, rejecting any affirmation that did not have empirical confirmation.