Manganism is a neurotoxic condition causing a parkinsonian-like symptom and results from excessive exposure to Manganese (Mn). Coenzyme Q10 and Epigallocatechin-3-gallate (EGCG) are promising neuroprotective agents. A low protein diet, a noteworthy problem in developing countries, leads to various health problems. So, this study was designed to assess the role of a low protein diet during induction and treatment of Manganism using Co-enzyme Q10, EGCG, or their combinations. Two sets of rats, normally fed (NF) (20% casein) and low protein diet-fed (10% casein) rats, were subdivided into five groups; control and four MnCl2(10mg/kg) groups, three of them were treated with either Co-enzyme Q10 (200mg/kg), EGCG (25mg/kg), or their combination. Four behavioral tests: grid, swimming, open-field, and Y-maze were done. Biochemical changes in monoamines, oxidative stress biomarkers, neuroinflammatory markers, BDNF, and Complex-I were also measured in the striatum. Moreover, serum albumin content and brain histopathological changes were examined. Revealing that MnCl2 induced an increase in catalepsy and a decrease in locomotor, emotionality, and exploratory activities with impairment of spatial memory, as well as delay in decision making and disruption in neuromuscular coordination and vigilance with changes in biochemical and histopathological examinations. All tested treatments enhanced most behavioral, biochemical, and histopathological impairments in the striatum, with a more pronounced effect of the combination. Low protein diet-fed rats showed slight improvement against Mn-induced neurotoxicity. In conclusion: Low protein diet showed pronounced improvement compared to the corresponding normally fed rats against Mn-induced neuronal degeneration either alone or treated.