The reduction in agricultural production due to the negative impact of insects and weeds, as well as the health and economic burden associated with vector-borne diseases, has promoted the wide use of chemicals that control these “enemies.” However, the use of these synthetic chemicals has been recognized to elicit negative impacts on the environment as well as the health and wellbeing of man. In this study, we presented an overview of recent updates on the environmental and health impacts of synthetic pesticides against agro-pest and disease vectors while exhaustive reviewing the potentials of natural plant products fromZanthoxylum species(Rutaceae) as sustainable alternatives. This study is expected to spur further research on exploiting these plants and their chemicals as safe and effective pesticide entities to minimize the impact of their chemical and synthetic counterparts on health and the environment.Graphical abstract