This thesis explores the role of circadian rhythm and sleep alterations in Parkinson’s disease (PD) through a multidisciplinary approach encompassing in vitro, clinical, and in vivo methodologies. The first study examined the circadian gene expression profile in the SN4741 dopaminergic progenitor cell line under differentiation conditions. Despite employing established synchronisation protocols, the cells exhibited limited rhythmicity, reflecting incomplete neuronal maturation and raising concerns about the suitability of this model for circadian research. The second study analysed self-reported data from a large PD patient cohort (Fox Insight) to investigate associations between sleep disturbances, mood, and cognitive outcomes. Results demonstrated a high prevalence of insomnia and excessive daytime sleepiness among PD patients, with significant correlations to depression, cognitive impairment, and reduced quality of life. These findings highlight the importance of recognising non-motor symptoms as integral to PD pathology. The third study used the mThy1-hSNCA mouse model to assess behavioural and molecular responses to circadian disruption. Transgenic mice showed age-dependent impairments in circadian re-entrainment, reduced photic responsiveness in the suprachiasmatic nucleus, and exacerbated mood-related behaviours under chronic jet lag conditions. Collectively, these studies provide converging evidence that circadian disruption interacts with ageing, sex and PD diagnosis to drive behavioural pathology. The findings advocate for integrating circadian assessments in PD diagnosis and management and support the development of chronotherapeutic strategies such as timed light exposure and circadian-informed medication scheduling. This work underscores the translational importance of circadian biology in understanding and treating PD.