In the era of green economy, trehalase inhibitors represent a valuable chance to develop non-toxic pesticides, being hydrophilic compounds that do not persist in the environment. The lesson on this topic that we learned from the past can be of great help in the research on new specific green pesticides. This review aims to describe the efforts made in the last 50 years in the evaluation of natural compounds and their analogues as trehalase inhibitors, in view of their potential use as insecticides and fungicides. Specifically, we analyzed trehalase inhibitors based on sugars and sugar mimics, focusing on those showing good inhibition properties towards insect trehalases. Despite their attractiveness as a target, up to now there are no trehalase inhibitors that have been developed as commercial insecticides. Although natural complex pseudo di- and trisaccharides were firstly studied to this aim, iminosugars look to be more promising, showing an excellent specificity profile towards insect trehalases. The results reported here represent an overview and a discussion of the best candidates which may lead to the development of an effective insecticide in the future.