Although synthetic pesticides are still used to control insect pests, greater efforts have been made to develop healthier and more environmentally friendly pesticides. Because of their insecticidal properties, botanical essential oils (EOs) are considered as promising alternatives to the use of synthetic insecticides. However, little is known about mechanisms underlying the insecticidal activity of most these natural compounds. In the present study, we evaluated the contact toxicity and the modes of action of the EO from Mentha arvensis against the granary weevil, Sitophilus granarius L. (Coleoptera: Curculionidae), a cosmopolitan insect pest that causes extensive damage to stored cereals. M. arvensis EO caused high contact toxicity in S. granarius adults, resulting in a rapid paralysis and rapid alteration of walking behavior. Our label-free quantitative proteomics approach revealed that M. arvensis EO induced dramatic physiological changes in exposed insects. The majority of the differentially expressed proteins (DEPs) were upregulated and are related to the development and functioning of the muscular and nervous systems, cellular respiration, protein synthesis, and detoxification. These results suggest that M. arvensis essential oil is capable of affecting a variety of biological processes, and shed light on the repair mechanisms put in place in surviving insects to counter the damage inflicted. This work opens new perspectives on the proposed mechanisms of insecticidal activity of a promising EO for controlling pests of stored cereals and may represent a first step in the development of novel bio-rational insecticides.