Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder (NDD) associated with the loss of dopaminergic neurons in the substantia nigra and subsequently has an effect on motor function and coordination. The pathology of PD is multifactorial, in which neuroinflammation and oxidative damage are the two of the main protagonists. Objectives: The present study aims to assess the potential antioxidant and anti-inflammatory effects of demethoxycurcumin (DMC), a natural derivative of curcumin, against rotenone-induced PD in rats. Materials and Methods: Rats were randomized and divided into six groups: control, rotenone (0.5 mg/kg/day, intraperitoneal in sunflower oil) treated for 7 days, rotenone and DMC (5, 10, and 20 mg/kg b.w) cotreated, and DMC (20 mg/kg b.w) alone treated groups. Results: Based on the dopamine concentration and biochemical estimations, the effective dose of DMC was selected and the chronic study was performed. At the end of the experimental period, behavioral studies and protein expression patterns of inflammatory markers were analyzed. Rotenone treatment led to motor dysfunctions, neurochemical deficits, and oxidative stress and enhanced expressions of inflammatory markers, whereas oral administration of DMC attenuated all the above. Conclusion: Even though further research is needed to prove its efficacy in clinical trial, the results of our study showed that DMC may offer a promising and new therapeutic lead for the treatment of NDDs including PD.