Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. Neuroinflammation and oxidative stress play an important role in the whole course of PD, which have been the focus of PD drug development. In our previous research, a series of N -salicylic acid tryptamine derivatives were synthesized, and the biological evaluation showed that the compound LZWL 02003 has good anti-neuroinflammatory activity and displayed great therapeutic potency for neurodegenerative disease models. In this work, the neuroprotective efficiency of LZWL 02003 against PD in vitro and in vivo has been explored. It was found that LZWL 02003 could protect human neuron cells SH-SY5Y from MPP + -induced neuronal damage by inhibiting ROS generation, mitochondrial dysfunction, and cellular apoptosis. Moreover, LZWL 02003 could improve cognition, memory, learning, and athletic ability in a rotenone-induced PD rat model. In general, our study has demonstrated that LZWL 02003 has good activity against PD in in vitro and in vivo experiments, which can potentially be developed into a therapeutic candidate for PD.