Neurodegenerative disorders (ND) such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and associated cognitive dysfunction are major concerns that add enormous social and financial burdens on society. Growing evidence suggests that Rho GTPase is the regulator of cellular morphology and an emerging driver for neurodegenerative disorders. The superfamily of Rho GTPase offers a potential target for therapeutic intervention through Rho and Rac. In this review, the molecular mechanism of Rho GTPase in the etiology of ND via modulation of signaling cascades like PI3K/Akt, GSK-3β, MEK and ERK ½ pathway have been discussed. Further, the neuroprotective role of statins as a Rho GTPase inhibitor has been emphasized. A comprehensive literature survey was done to explicate the mechanism of Rho GTPase in neurological disorders and in vivo, in vitro and clinical studies were correlated with the inhibitory effect of statin on Rho GTPase. Based on the current review, it was hypothesized that the statins are potent inhibitors of Rho GTPase and can be efficient in the management and treatment of ND and associated cognitive dysfunction modulation of apoptosis, neuronal death, inflammatory cascade and oxidative stress that offers neuroprotection. To date, no targeted Rho inhibitor has been clinically approved. Thus, there exists a full window of opportunity for designing, leading optimization and development of Rho inhibitors. The use of techniques like molecular docking and crystal structure study to establish drug-ligand interaction between Rho GTPase and statins to increase its specificity and efficacy in the management of neurological disorders is crucial and urgent.