BACKGROUND: Parkinson's disease is a progressive neurodegenerative disease characterized by clinical motor signs and non-motor symptoms that severely impact quality of life. There is an urgent need for therapies that might slow, halt or even reverse the progression of existing symptoms or delay the onset of new symptoms. Photobiomodulation is a therapy that has shown potential to alleviate some symptoms of Parkinson's disease in animal studies and in small clinical trials. OBJECTIVE: To assess long-term effectiveness of photobiomodulation therapy in a cohort of Parkinson's disease individuals after five years of continuing therapy. METHODS: Eight participants of the initial 12 in a previously published study agreed to be reassessed after five years. Seven of these participants had continued home-based, self-applied photobiomodulation therapy three times per week for five years. One participant had discontinued treatment after one year. Participants were assessed for a range of clinical motor signs, including MDS-UPDRS-III, measures of mobility and balance. Cognition was assessed objectively, and quality of life and sleep quality were assessed using self-reported questionnaires. A Wilcoxon Signed Ranks test was used to evaluate change in outcome measures between baseline (before treatment) and after five years, with the alpha value set to 0.05. RESULTS: Of the seven participants who had continued photobiomodulation therapy, one had a preliminary diagnosis of multisystem atrophy and was excluded from the group analysis. For the remaining six participants, there was a significant improvement in walk speed, stride length, timed up-and-go tests, tests of dynamic balance, and cognition compared to baseline and nonsignificant improvements in all other measures, apart from MDS-UPDRS-III, which was unchanged and one measure of static balance (single leg stance, standing on the unaffected leg with eyes open) which declined. Five of six participants either improved or showed no decline in MDS-UPDRS-III score and most participants showed improvement or no decline in all other outcome measures. No adverse effects of the photobiomodulation therapy were reported. CONCLUSIONS: This study provides a signal that photobiomodulation therapy might safely reduce important clinical motor signs and non-motor symptoms in some Parkinson's disease patients, with improvements maintained over several years. Home-based photobiomodulation therapy has the potential to complement standard therapies to manage symptoms and potentially delay Parkinson's symptom progression. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, registration number ACTRN12618000038291p, registered on 12/01/2018.