Updated project metadata. This study aimed at integrating metabolomics and proteomics data for a comprehensive view of the molecular targets of intervention of protein extracts from Tenebrio molitor in treating hypertension. Serum samples from spontaneously hypertensive rats and Wistar Kyoto rats were analyzed using a quantitative metabolomics and label-free proteomics approach based on liquid chromatography coupled with high resolution mass spectrometry (LC-HRMS). Among deregulated metabolites and proteins in hypertensive rats, we found 15 metabolites and 17 proteins that were restored by supplementation with Tenebrio molitor protein extract. The combination of metabolomics and proteomics provided useful data to uncover the molecular targets of intervention and the underlying functional mechanism of Tenebrio molitor protein extract in an animal model such as spontaneously hypertensive rats. The results suggested that Tenebrio molitor supplementation could effectively treat hypertension, partially by regulating proteins and molecules mainly involved in biological pathways associated to angiotensinogen-angiotensin, Serin protease inhibitors, kallikrein–kinin, reactive oxygen scavenging, and lipid peroxidation.