This study investigated the toxicological effect of cadmium and zinc oxide nanoparticles (ZnONPs) in land snails (Helix aspersa). Snails were exposed for 28 days to cadmium combined with ZnONPs at increasing concentrations (250, 750, 2250, 6750, and 20250mg/kg dry weight of soil “dwt”). Exposure to Cd and ZnONPs mixtures resulted in slight decrease inbody weight, and weights of vital organs (hepatopancreas, kidney, and smooth muscle). Oxidative stress effect was evidenced by significant increase in malondialdehyde (MDA, a marker of oxidative stress) content, and decrease in glutathione (GSH, an antioxidant) content, and the enzymatic activity of catalase (CAT), glutathione S-transferase (GST) and the neurotransmitter enzyme acetylcholinesterase (AChE) in hepatopancreas and kidney tissues. Histological analysis revealed gradual histological alterations to the kidney and hepatopancreas in Cd/ZnONPs mixture treatments. These findings suggest that and Cd and ZnONPs mixtures caused a toxicity on the antioxidant defense system and physiology of Helix aspersa.