Parkin and alpha‑synuclein (α‑syn) are two key proteins involved in the pathophysiology of Parkinson’s disease (PD). Oligomerization/ aggregation and excessive secretion of α‑syn contributes to PD through free radical stress, mitochondrial impairment, and synaptic dysfunction. Parkin, an E3 ubiquitin ligase, is considered to be a pleiotropic, neuroprotective protein that modulates metabolic turnover and the accumulation of α‑syn. This is in addition to parkin’s role in counteracting the more distant effects of α‑syn on cellular survival by altering proteasomal, autophagic, and calpain‑mediated protein degradation pathways that can reduce α‑syn levels. Moreover, parkin regulates mitochondrial turnover, cell survival, and immune phenomena – processes that are all known to be disturbed in PD. In addition, parkin might have an impact on the spreading and propagation of α‑syn by controlling its post‑translational modifications. On the other hand, recent research has shown that α‑syn oligomers affect the expression, post‑translational modification, and activity of parkin. This review focuses on the molecular mechanisms of cross‑talk between parkin and α‑syn in PD. The physical and functional interactions between α‑syn and parkin, which have been incompletely characterized to‑date, may present a new therapeutic avenue in PD and related synucleinopathies. The development of effective, clinically feasible modulators may offer great hopes for the therapy of PD.