Dopaminergic neuron loss and alpha-synuclein aggregation brought on by an excess of reactive oxygen species (ROS) are linked to Parkinson's disease (PD). The pharmacological characteristics of hesperidin (HES), including its anti-inflammatory, anti-atherosclerosis, anti-diabetic, anti-cancer effects have been the subject of much recent research. However, its possible neuroprotective effects on SH-SY5Y cells, a cellular PD model, caused by the neurotoxic MPP+, have not been studied. In this investigation, we postulated that antioxidant activities may scavenge ROS, hence mediating neuroprotective benefits against MPP+-induced oxidative stress parameters. Here, HES pre-treatment could attenuate MPP+-induced neuronal cell death, which was reflected by decreasing the levels of ROS, Total Oxidant Status (TOS) and inflammation. Moreover, HES led to increased levels of the antioxidant enzyme GSH and TOS. According to this study, HES demonstrated notable neuroprotective benefits against MPP+-induced SH-SY5Y cell death in vitro. Our findings demonstrate that HES may be a valuable adjunct for Parkinson's disease prevention.