Objective: Cinnamaldehyde may be responsible for some health benefits of cinnamon such as its neuroprotective effects. We aimed to investigate the cinnamaldehyde neuroprotective effects against amyloid beta (Aβ ) in neuronal SHSY5Y cells and evaluate the contribution of N-methyl-D-aspartate (NMDA), ryanodine, and adenosine receptors and glycogen synthase kinase (GSK)-3β , to its neuroprotective effects. Materials and Methods: After seeding the cells in 96-well plates, adenosine (20, 40, 80, and 120 µ M), NMDA (20, 40, 80, and 120 µ M), and dantrolene (as a ryanodine receptor antagonist; 2, 4, 6, 8, and 16 µ M) were added to the medium containing Aβ 25-35 and/or cinnamaldehyde. The 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide method was used to assess neurotoxicity and western blot to measure the GSK-3β protein level. Results: Cinnamaldehyde (15, 20, 23, and 25 μ M) significantly reversed Aβ-induced toxicity in SHSY5Y neuronal cells. Adenosine (20, 40, 80 and 120 μ M) inhibited the neuroprotective effects of cinnamaldehyde (15 μ M). NMDA (20, 40, 80, and 120 μ M) reduced cinnamaldehyde (15 and 23 μ M) neuroprotective effects against Aβ neurotoxicity. Dantrolene (2, 4, 8, and 16 μ M) significantly reduced cinnamaldehyde (15 μ M) neuroprotective effects. Cinnamaldehyde (15 and 23 μ M) suppressed the Aβ induced increment of GSK-3β protein level. Conclusion: NMDA and adenosine receptors suppression together with ryanodine receptors stimulation may be relevant to cinnamaldehyde neuroprotective effects against Aβ neurotoxicity. Moreover, the inhibition of GSK-3β may contribute to the cinnamaldehyde neuroprotection.