The increasing use of synthetic chemical herbicides has resulted in environmental, human and animal health issues. This has also led to the development of herbicide resistance in weed populations. The use of essential oils (EOs) can contribute to the development of effective, eco-friendly and nature-based alternatives to these chemical products due to their phytotoxicity and multisite action. Our study aimed to evaluate the proteomic response of Arabidopsis thaliana (A. thaliana) leaves to the application of a cinnamon essential oil (CEO) emulsion. The results showed that the application of CEO emulsion at a concentration of 6% severely impacted the proteomic profile of A. thaliana, especially for membrane proteins and those involved in the photosynthesis process. Interestingly, 40 proteins were identified and listed as the most differentially accumulated proteins in the leaves of A. thaliana. CEO decreased the expression of all the proteins associated with catabolism and anabolism processes while simultaneously increasing the expression levels of proteins involved in the response to oxidative stress. Overall, these findings allowed us to obtain a global view of the proteome response to CEO, opening promising perspectives for the development of natural herbicides, especially given the low probability of developing resistant weed populations.