Introduction: Oxidative stress might be one of the contributing mechanisms to motor neurons apoptosis in several neuronal diseases. Silymarin, extracted from milk thistle seeds, and artichoke flavonoids were reported as potent antioxidants with a high ability for attenuating oxidative stress. Objective: This study was conducted to investigate the effects of silymarin and artichoke flavonoids on the apoptosis of motor neurons in cultured spinal cord slices. The thoracic region of the spinal cord of adult mice was sliced, and divided into four groups: 1) slices at 0-hour, 2) control slices, 3) slices treated with silymarin (96.88μg/ml), and 4) slices treated with artichoke flavonoids (10μg/ml). The slices from groups 2-4 were cultured for 6 hours, then fixed and sectioned. Morphological features of apoptosis were evaluated in the motor neurons using Hoechst and propidium iodide staining. In addition, malondialdehyde (MDA) and ferric reducing antioxidant power (FRAP) were assessed to evaluate lipid peroxidation and total antioxidant capacity, respectively. Results: After 6 hours, cultured motor neurons displayed morphological features of apoptosis. At this time point, the levels of MDA and FRAP were respectively increased and decreased compared to the 0-hour slices. The administration of silymarin and artichoke flavonoids could delay apoptosis in the cultured motor neurons. In addition, silymarin but not artichoke flavonoids compensated for the levels of MDA and FRAP compared to the control group. Conclusion: Oxidative stress might be the mechanism involved in the apoptosis of motor neurons in cultured spinal cord slices, while silymarin and artichoke flavonoids with their antioxidant properties could delay the apoptosis of these motor neurons, introducing them as antiapoptotic compounds.