PINK1 kinase plays a crucial role in mitochondrial quality control through the initiation of mitophagy, and its dysfunction is genetically linked to Parkinson's disease. In this study, we evaluated the effects of published PINK1-activating compounds using pS65-Ub and mitophagy assays, confirming that these compounds induce PINK1-mediated mitophagy activation. Notably, we observed that the compounds synergistically enhanced mitophagy in conjunction with mitochondrial toxins Antimycin and Oligomycin. The potency of mitophagy induction was influenced by the concentration of the co-treating toxins; higher toxin concentrations reduced the required dose of PINK1 activators to increase mitophagy. Additionally, the compounds exhibited mitochondrial toxicity in Glucose-Galactose, TMRM, and Seahorse assays. The PINK1-activating compounds also synergized with Antimycin but not with Oligomycin in the Glucose-Galactose assay. We additionally replicated a previously reported reduction in alpha-synuclein (aSyn) pathology in a primary rodent neuronal model. Collectively, these findings suggest that the PINK1-activating molecules induce PINK1 and mitophagy activation while also mitigating aSyn pathology. However, further studies are needed to determine whether these compounds bind directly to PINK1 or interact with an upstream mitochondrial factor to facilitate PINK1 activation.