This study aimed to identify the total proteome of Hydra vulgaris, a freshwater polyp representative of the phylum Cnidaria. This organism, known for its organized nerve net, has been a favoured model due to its unique regeneration capabilities, simple bilayer architecture separated by a mesoglea, and limited cell types. While vertebrate models offer insights into molecular signaling, invertebrate like Hydra have been instrumental in uncovering the evolutionary roles of various molecules. Despite advances in genomic analyses of Hydra, a comprehensive proteomic analysis has been lacking. Here, we explored the proteome of Hydra vulgaris using a combination of gel electrophoresis and nanoflow liquid chromatography-mass spectrometry, identifying over 5,200 proteins across all cellular components. This proteomic analysis helps gain insight into the evolutionary origins and ancestral functions of proteins involved in contemporary diseases such as Alzheimer's disease or inherited retinal dystrophies. This analysis led to the identification of proteins corresponding to transporter proteins, or to endoplasmic reticulum. Such are ATPase, calcium-binding or retinal proteins with 4 linked to photoreceptors and 6 implicated in Alzheimer disease. The data set provided in this article describes the proteins identified in the body of Hydra and the processes and functions associated with a selection of them.