It has been estimated that there will be 930 million Parkinson's disease (PD) patients in 2030 in the whole world. However, no therapy has been effective for PD until now. Only levodopa is the available primary drug for the treatment of motor symptoms. Therefore, it is an urgent task to develop new drugs to inhibit the progression of PD and improve the quality of the patient's life. Dyclonine which was found to have antioxidant activity and would benefit patients with Friedreich's ataxia, is a commonly used local anesthetic. Here, we reported that dyclonine improved the motor ability and loss of dopaminergic neurons in the rotenone-induced Drosophila PD model for the first time. Furthermore, dyclonine upregulated the Nrf2/HO pathway, decreased the ROS and MDA levels, and inhibited the apoptosis of neurons in the brain of PD model flies. Hence, dyclonine might be an attractive FDA-approved drug for the exploration of effective PD therapy.