Objective To investigate the neuroprotective effect of Dendrobium nobileLindl (DNL) extract in a Caenorhabditis elegans (C.elegans)model of Parkinson’s disease (PD). Methods C. elegans NL5901 and 6 hydroxydopamine (6-OHDA)induced N2, BZ555, PD4521, and CB7272 C. elegans strains were treated with DNL 7.5, 15, and 30 mg/L. The survival rate, basal slowing response rate, α-synuclein (α-syn) aggregation, dopaminergic neurons (DNs), mitochondrial distribution density of body wall muscle cells, and protein levels in the membrane were observed. In addition, reactive oxygen species(ROS), superoxide dismutase(SOD) and glutathione (GSH) in 6-OHDA induced N2 was detected to explore the effect of DNL on the antioxidative stress ability of PD C. elegans models. Results Compared with that in the model group, the DN fluorescence intensity was significantly increased in nematodes treated with DNL and levodopa(L-DOPA) (P<0.05, P<0.0001), α-syn aggregation was significantly decreased (P<0.05, P<0.001, P<0.0001), the basal slowing rate (P<0.05, P<0.01, P<0.001), mitochondrial density (P<0.05, P<0.01, P<0.001), mitochondrial intima protein content (P<0.05, P<0.001, P<0.0001), SOD content (P<0.05), and GSH content were all increased. The ROS content was reduced in nematodes(P<0.01). The lifespans of N2 wild-type and PD C. elegans models were prolonged after DNL treatment (P<0.05, P<0.01, P<0.001). Conclusions DNL can effectively improve motor paralysis in a C. elegans PD model, improve DN degradation, inhibit α-syn aggregation and neuronal damage, increase the antioxidative stress ability, and slow the aging process in C. elegans.