The aim of this study was to investigate the possible therapeutic effects of curcumin (CUR), against acrylamide (AA)-induced toxic effects on Leydig cells. The AA and CUR-treated cells were evaluated for cell viability, lipid peroxidation, reactive oxygen species (hydroxyl radical and hydrogen peroxide), antioxidant levels (glutathione peroxidase, glutathione-S-transferase, and catalase), apoptosis/necrosis rates and phosphorylation status of mitogen-activated protein kinases (MAPKs). Leydig cells were exposed to four concentrations of AA (1, 10, 100, 1000 mu M) in the presence and absence of CUR (2.5 mu M) for 24 hours. According to the present result, AA concentration-dependently, increased the oxidative stress parameters and suppressed the antioxidant enzyme levels, meanwhile induced apoptosis and activated the phosphorylation of extracellular signal-regulated kinase, p38, and c-Jun NH2-terminal kinase. Moreover, CUR ameliorated the detrimental effects of AA. Thus, AA-induced apoptosis through activation of the MAPK signaling pathway and CUR has a protective effect against AA-induced damage in Leydig cells.