Objective To investigate the neuroprotective effect of Dendrobium nobile Lindl (DNL) in mice with 1-methyl-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson’s disease (PD). Methods After establishment of the MPTP-induced subacute PD mouse model (30 mg MPTP / ( kg·day) i.p, 7 d), the effects of DNL on the motor dysfunction in PD mice were evaluated by gait analysis, the pole test, suspension test and open field test. The effects of DNL on the expression levels of tumor necrosis factor-α (TNF-α), interleukin-6 ( IL-6) and interleukin-1β ( IL-1β) in PD mice were determined by ELISA. The effects of DNL on the expression levels of caspase-3 and caspase-9 in PD mice were assessed by Western blot. Results Compared with the control group, gait indexes, such as the propulsion index and duty cycle, were significantly changed in the model group (P<0.05) compared with model group, whereas Madopar and DNL (100, 200 and 300 mg / kg) groups showed significant improvements (P<0.05, P<0.01 and P<0.001). In the pole test, compared with the control group, climbing in the top half of the pole time and total time of the model group were significantly increased (P<0.01 and P<0.001), but the time of turn around and the time of the lower half of the pole were not changed significantly (P>0.05). Compared with model group, the DNL (300 mg / kg) group showed improvement in the top half of the pole time (P<0.05), but Madopar and DNL ( 100 and 200 mg / kg) groups had no significant improvement (P>0.05). In the suspension test, compared with the control group, the suspension score of the model group was significantly decreased (P<0.05) compared with that of the model group and the suspension score of the DNL (300 mg / kg) group was increased (P<0.05), but there was no significant improvement in Madopar and DNL (100 and 200 mg / kg) groups (P>0.05). Compared with the control group, the levels of TNF-α, IL-1β, IL-6, caspase-3 and caspase-9 were increased in the striatum of mice in the model group (P<0.05, P<0.001) compared with model group and those in the DNL (300 mg / kg) group were significantly lower (P<0.05), but there were no significant differences in the content of cortex among the groups (P>0.05). Conclusions DNL significantly improved MPTP-induced behavioral changes in PD mice, reduced the inflammatory response and neuronal apoptosis in brain tissue, and has a good potential for the development of PD drugs and functional food.