Context Levodopa combined with traditional Chinese medicine has a synergistic effect on Parkinson's disease (PD). Recently, we demonstrated that Nardostachys jatamansi (D. Don) DC. [syn. Patrinia jatamansi D.Don, N. grandiflora DC.] (Valerianaceae) (NJ) can alleviate PD. Objective To explore the synergistic effect of NJ combined with levodopa against PD. Materials and methods The PD model was established by injecting rotenone. Eighty-four Sprague-Dawley rats were randomly divided into seven groups: sham, model, different doses of NJ (0.31, 0.62, or 1.24 g/kg) combined with levodopa (25 mg/kg), and levodopa alone (25 and 50 mg/kg) groups. The synergistic effect of the combination was investigated by pharmacodynamic investigation and detection of expression of nuclear factor erythro2-related factor 2 (Nrf2) and NLR family proteins containing Pyrin-related domain 3 (NLRP3) pathways. Results Compared with the model group, NJ + levodopa (1.24 g/kg + 25 mg/kg) increased the moving distance of PD rats in the open field (2395.34 & PLUSMN; 668.73 vs. 1501.41 & PLUSMN; 870.23, p < 0.01), enhanced the stay time on the rotating rod (84.86 & PLUSMN; 18.15 vs. 71.36 & PLUSMN; 17.53, p < 0.01) and the combination was superior to other treatments. The synergistic effects were related to NJ + levodopa (1.24 g/kg + 25 mg/kg) increasing the neurotransmitter levels by 38.80%-88.67% in PD rats, and inhibiting oxidative stress and NLRP3 pathway by activating Nrf2 pathway. Discussion and conclusions NJ combined with levodopa is a promising therapeutic candidate for PD, which provides a scientific basis for the subsequent clinical combination therapy of levodopa to enhance the anti-PD effect.