An Organophosphorus Nerve agent, VX [(O-Ethyl S-diisopropylaminomethyl) methylphosphonothiolate] compound interfere with acetylcholine signaling by targeting the AChE enzyme. Studies suggest that in nerve agents poisoning, non-cholinergic effects are also responsible for damages in peripheral tissues including long term damage in brain. Present study reports cholinergic and non-cholinergic effects of VX poisoning and their reversal by combinational therapy using conventional antidotes atropine sulphate and 2-PAM chloride along with N-acetyl cysteine (NAC) as an antioxidant. In present study, it was attempted to prevent the toxic effects of nerve agent poisoning by using combination therapy with NAC so as to prevent both cholinergic and non-cholinergic damages. NAC was chosen as this molecule is available as approved drug for medical conditions including oxidative damage and mucolysis. Results of the study showed that NAC adjuvant treated groups had better recovery not only in cholinesterase level, it maintained intracellular and tissue GSH level, reduced in ROS generation and lipid peroxidation. Cell cycle analysis and histopathological results showed NAC could able to protect the damage. In conclusion it was found that combination therapy of antioxidant; NAC along with standard atropine-oxime treatment is helpful in reducing the cholinergic and oxidative stress mediated toxicity induced by VX.