The objective of this research is the driving performance profiles analysis of drivers with Parkinson’s disease (PD), on the basis of a driving simulator experiment, in which healthy and PD participants drive in different driving scenarios, following a thorough neurological and neuropsychological assessment. The driving scenarios include driving in rural area in low and high traffic volumes and driving in motorway. The driving performance of PD is compared to that of healthy controls by means of a generalized linear model (GLM) which was developed in order to estimate the effect of the examined disease in driving behaviour. In this specific research, a sample of 62 participants is statistically analysed (21 PD and 41 control drivers). Various driving performance measures are examined, including speed, lateral position, steering angle, headway, reaction time at unexpected events, accident probability, some in terms of their mean values and some in both their mean values and their variability. Moreover, another factor indicating driving behaviour is examined: manoeuvres through work-zone segments in motorway. The results suggest that Parkinson’s disease do affect driving behaviour in several ways. More specifically, PD drivers drive at significantly lower speeds and with larger headway compared to healthy drivers. Moreover, they appear to have worse reaction times, are more likely to have accident inside a work-zone segment, have difficulties in positioning the vehicle in the lane and have difficulties in dealing with demanding tasks.