Parkinson's disease (PD) ranks as the second most neurodegenerative disease characterized by loss of neurons, bradykinesia, anosmia, sleep disorder, and motor deficiency with increased global prevalence. Here, we have analyzed daidzein's neuroprotective functions in in vitro and in vivo models of PD. BV2 microglial cells induced with lipopolysaccharide (LPS) and C57BL6 mice induced with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) were used in this study to investigate neuroprotective functions of daidzein. BV2 cells induced with LPS do not exert and significant (p < 0.05) reduction in cell viability up to concentration range (5–100 µM/ml). Furthermore, LPS exposed BV2 microglia exhibited significantly (p < 0.05) increased NO production, pro-inflammatory mediators PGE2, interleukin-6 (IL6), and interleukin-1β (IL-1β) levels. Treatment with daidzein (10, 25, and 50 µM/ml) to LPS-induced BV2 microglia exhibited significantly (p < 0.05) decreased NO, pro-inflammatory mediators PGE2, IL6, and IlL-1β. Similar to the in vitro results, C57BL6 mice induced with MPTP showed defects in motor functions as observed from altered forelimb and hindlimb footprint analyses, grip strength, and perturbed motor coordination observed via rotarod tests. Additionally, levels of dopamine were significantly reduced, and pro-inflammatory mediators tumor necrosis factor alpha (TNF-α), IL-1β, IL6 were found to be increased in MPTP-induced C57BL6 PD mice. Administering daidzein significantly restored the functional levels of dopamine and pro-inflammatory mediators TNF-α, IL-1β, IL6 to near normal physiology as seen in healthy C57BL6 mice controls. Similarly, daidzein treatment to PD mice also restored the histological architecture to near normal levels as in control mice. Together, our results collectively endorse the neuroprotective functions of daidzein as observed from our initial studies, and further studies aimed at investigating daidzein's ability in regulating the catecholamine synthesis pathway to protect substantia nigra pars compacta (SNpc) neurons are in focus.