Nanoparticles based drug delivery system offers an alternative strategy to overcome several therapeutic limitations of various human ailments, particularly in age-linked Alzheimer's disease. Results of our previous cell-free studies indicated that α-bisabolol loaded solid lipid nanoparticles (ABS) significantly inhibited the aggregation of Aβ. The present study intended to evaluate the neuroprotective effect of ABS against Aβ induced toxicity in Neuro-2a cell lines. The results of in vitro cell line study revealed that pretreatment of Neuro-2a cell lines with ABS (5 & 10 μg/ml) significantly suppressed the production of free radicals such as reactive oxygen species (ROS)/reactive nitrogen species (RNS), and also augmented the ROS mediated macromolecular damages and loss of mitochondrial membrane potential induced by toxic Aβ peptide when compared to the standard drug donepezil (50 μg/ml). Moreover, reduced β-secretase, caspase-3, and cholinesterase activities were observed in the cells pretreated with ABS, which clearly evidenced the neuroprotective effect of ABS. Reduced expression of Bax and induced expression of Bcl-2 proteins observed through western blot analysis and live/dead cell viability analysis of Neuro-2a cells through confocal microscope further validated that ABS protects the cells from Aβ induced apoptosis. Taken together, the outcome of the present study signifies the neuroprotective effect of ABS against the Aβ induced toxicity in in vitro model of Neuro-2a cells.