Parkinson's disease (PD) is a neurodegenerative disorder characterized by the intracellular accumulation of α-synuclein (α-syn) protein within Lewy bodies, which are hallmark neuropathological lesions of α-synucleinopathies. Network analysis, incorporating prior knowledge such as biological pathways and gene expression data from patients with PD, was used to identify the pharmaceutically active ingredients of MT101–5 and elucidate their mechanisms of action related to proteasome activation in PD. To validate the artificial intelligence (AI) model's prediction that API-mediated α-syn aggregate clearance occurs through enhanced proteasome activity, we employed a reporter-based screening to assess proteasome function within the ubiquitin-proteasome system. Our findings demonstrated that diterpenes derived from Genkwae Flos in MT101–5 inhibited α-syn fibril formation by restoring proteasome activation through Nurr1 activity. Two diterpenoids mitigated behavioural deficits and dopaminergic neuron loss in mice subjected to subacute MPTP administration (30 mg/kg/day for 5 days). These results provide preliminary evidence supporting the therapeutic potential of the active ingredients in MT101–5 for the prevention or treatment of PD.