Parkinson’s disease is a common movement disorder associated primarily with oxidative stress-mediated degeneration of dopaminergic neurons. Earlier studies showed that Sorghum bicolor-based supplement (SbS) exhibited antioxidant and neuroprotective activities and might likely rescue the death of dopaminergic neurons in Parkinson’s disease. This study examined the effect of SbS on rotenone-induced Parkinsonian-like motor deficits in rats and the involvement of oxidative stress and pro-inflammatory cytokines. Rats were divided into six groups and treated orally with sunflower oil (vehicle-control), rotenone (2.5 mg/kg) alone or in combination with each dose of SbS (50, 100, and 200 mg/kg) and carbidopa (10 mg/kg) on an alternate day for 28 days. The changes in motor functions were evaluated on day 28 and the brain concentrations of oxidative stress biomarkers and pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6) were determined. Rotenone caused motor deficits by impaired locomotor activity in the open field test and induced catalepsy in the bar test, which were attenuated by SbS. Rats pretreated with SbS had reduced brain levels of malondialdehyde, nitrite, and pro-inflammatory cytokines compared to rotenone controls. 100 mg/kg and 200 mg/kg SbS mitigated rotenone-induced depletion of reduced glutathione and antioxidant enzymes in the rat brain. The results suggest that SbS ameliorated rotenone-induced Parkinsonian-like motor dysfunctions by reducing neuronal oxidative stress and pro-inflammatory cytokines in rats.