Objective To investigate the neuroprotective effect of total flavones of Dracocephalummoldavica L. (TFDM) on MPTP-induced Parkinson’s disease (PD) model mice. Methods After the MPTP-induced PD model was established, the effect of TFDM on motor function was evaluated by Rota Rod and climbing pole performance. Expression of oxidative stress factor superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were detected by ELISA. The expression of tyrosine hydroxylase (TH) and apoptosis-related proteins caspase-3, Bcl-2, and Bax were detected by immunohistochemistry and western blot. Results Behavioral evaluation showed that TFDM therapy significantly increased the fall latency time (P< 0. 05) and decreased the climbing time (P< 0. 05). ELISA showed that TFDM therapy significantly reduced MDA content (P< 0. 01), and the expression of SOD and GSH-Px were significantly increased (P<0.05). Immunohistochemistry and Western blot showed increased TH, Bcl-2, Bcl-2/ Bax protein expression (P< 0. 05), and decreased caspase-3 and Bax expression (P< 0.05). Conclusions TFDM improved motor dysfunction and reduced oxidative stress injury and dopaminergic neuron loss in PD model mice. The neuroprotective effect may be mediated by inhibiting caspase-3 activity, upregulating Bcl-2, and downregulating the expression of Bax.