Despite the growing body of research, definitive evidence on the effectiveness of depuration in detoxifying aquatic organisms and its associated biochemical impacts remains limited. This study evaluates the potential of depuration to mitigate anthropogenic pollution in Mytilus galloprovincialis (Mollusca, Bivalvia) by examining various biomarkers, including glycogen reserves, and protein metabolism, as well as their correlation with lactate dehydrogenase activity (LDH) and protein carbonyls (PCs). Adult M. galloprovincialis specimens were collected from Sidi Salem, a site heavily polluted with a range of contaminants, notably heavy metals, were transferred to aquaria containing seawater from a clean reference site (El Hnaya) for an 8-day depuration period. Samples were taken at 0, 2, 4, 6, and 8 days. Depuration had a significant effect on all biomarkers, which remained unchanged between non-depurated and depurated individuals. Glycogen and protein levels increased substantially after 8 days of depuration, while LDH activity content and PCs showed significant reductions after 6 and 8 days, respectively. These results suggest that depuration can effectively reduce oxidative stress in contaminated bivalves, contributing to improved physiological health.