Quantum dots (QDs) have attracted increasing interest in bioimaging and sensing. Here, we report a biosensor of complex I using ubiquinone-terminated disulphides with different alkyl spacers (QnNS, n = 2, 5 and 10) as surface-capping ligands to functionalise CdSe/ZnS QDs. The enhancement or quenching of the QD bioconjugates fluorescence changes as a function of the redox state of QnNS, since QDs are highly sensitive to the electron-transfer processes. The bioconjugated QnNS-QDs emission could be modulated by complex I in the presence of NADH, which simulates an electron-transfer system part of the mitochondrial respiratory chain, providing an in vitro and intracellular complex I sensor. Epidemiological studies suggest that Parkinson's patients have the impaired activity of complex I in the electron-transfer chain of mitochondria. We have demonstrated that the QnNS-QDs system could aid in early stage Parkinson's disease diagnosis and progression monitoring by following different complex I levels in SH-SY5Y cells.