Scorpion’s toxins have attracted attention as a treatment for diverse neurological diseases related to myelin loss. This study aimed to investigate the effect of kaliotoxin2 (KTX2), a potassium-channel blocker from Androctonus australis hector venom on cuprizone model of demyelination. Results showed that KTX2 modulates the behavioral functions, the demyelination, and reduces the recruitment of microglia, astrocytes, and granulocyte in the brain. KTX2 modulates the inflammatory response by increasing the IL-10 release, attenuating NFκB activation, and decreasing the oxidative stress markers and IL-6 levels. Results highlight the modulating effects of KTX2 on cuprizone model and confirm its therapeutic potential in demyelination diseases. Highlights Kaliotoxin2 (KTX2) prevents the excessive reduction in body weight gain and modulate motor coordination disorder induced by cuprizone. KTX2 from Aah venom protect myelin from the destructive effects of cuprizone. KTX2 inoculation to the CNS reduce microglia, astrocytes and granulocyte infiltration in the brain. KTX2 increases the production of the anti-inflammatory cytokine IL-10 and attenuates the activation of NFκB. KTX2 counterbalances cuprizone-induced brain unbalance of neurochemical redox parameters.