Chios mastic gum (CMG), derived from the resin of the Pistacia lentiscus has long been considered a natural remedy in the Mediterranean region. Its anti-inflammatory and an-tioxidant properties have garnered increasing attention from scientists and consumers over recent decades. While substantial evidence supports CMG's efficacy in preventing and treating common health disorders and its potential as a cancer cell inhibitor, the un-derlying molecular mechanisms remain poorly understood. In this study, we utilized zebrafish embryos as a model organism to investigate the molecular pathways affected by CMG administration. Embryos were exposed to non-toxic CMG concentrations for 3 to 96 hours post-fertilization. LC-HRMS proteomics, combined with enrichment analysis, re-vealed key biological pathways, exemplified by oxidative phosphorylation (OxPhos), elec-tron transport chain (ETC), and tricarboxylic acid cycle (TCA). The latter highlights the benefits of CMG administration in energy generation and cytoskeletal integrity. From the plethora of identified proteins, hierarchical clustering revealed three main antioxidant proteins as upregulated, namely copper-zinc superoxide dismutase, thioredoxin-disulfide reductase, and catalase, confirming the contribution of CMG to the enhancement of zebrafish's antioxidant defense.