Background <p>Parkinson’s disease (PD) is a complex neurodegenerative disorder characterized by dopaminergic neuronal loss and α-synuclein accumulation, which leads to progressive motor and non-motor impairments. Conventional treatments are symptomatic and lack disease-modifying potential; however, gene therapy (GT) technologies are emerging as promising approaches for treating PD. Effective drug delivery systems are central to the success of GT in overcoming challenges, such as the blood-brain barrier, immunogenicity, and targeting specificity.</p> Area covered <p>This review highlights advancements in GT delivery systems for PD, focusing on viral and non-viral vector delivery systems. Key therapeutic strategies are discussed, such as dopamine enhancement, neuroprotection using neurotrophic factors, ribonucleic acid (RNA) interference, and clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (CRISPR/Cas9) genome editing. Clinical progress in targeting PD-related genes, including SNCA and LRRK2, underscores the potential of GT delivery systems for slowing disease progression. Challenges such as immune responses, limited transgene capacity, and targeting specificity have been addressed alongside innovations in non-viral vectors to overcome these limitations.</p> Expert opinion <p>Advances in GT delivery systems are driving a paradigm shift in PD treatment by enabling targeted delivery of therapeutic genes to the brain, potentially modifying disease pathology. While challenges remain, emerging tools, such as CRISPR interference and hybrid delivery approaches, provide promising solutions. However, further translational research must address challenges such as long-term stability, consistent transgene expression, and large-scale production. Optimized delivery systems hold the key to unlocking the full potential of GT in the treatment of PD and related neurodegenerative diseases.</p>