Over the past 200 years, Parkinson's disease (PD) has remained an insurmountable challenge. Despite the existence of numerous therapeutic drugs, there are still not enough treatments in the face of the complex pathogenesis of PD. Therefore, the search for more effective therapeutic drugs for PD has extremely important practical significance. Procyanidin (PC), widely found in plants such as grapes, is a bioflavonoid antioxidant with a special molecular structure that can effectively remove free radicals in the human body. To explore its possible mechanism in PD, we used 6-hydroxydopamine (6-OHDA, 8 μg) to mimic dopaminergic (DA) neuronal damage and validated this model in vivo and in vitro. in vivo, we detected an effect of PC (60 mg/kg) on the behavioural changes exhibited in 6-OHDA model rats, the number of DA neurons and the phosphorylation of protein kinase B (Akt). in vitro, we detected changes in cell viability, mitochondrial membrane potential (MMP) and total superoxide dismutase (SOD) and explored the role of PC (50 μM) by inhibiting the phosphoinositide 3-kinase (PI3K)/Akt signalling pathway with LY294002 (20 μM). The present study demonstrates that PC plays a protective role against 6-OHDA-induced neurotoxicity, which may be mediated through the activation of the PI3K/Akt signalling pathway. This study indicates a potential use for PC in the treatment and prevention of PD.