In recent years, probiotics, as a class of biologically active microorganisms, have increasingly attracted attention for their potential in treating neurodegenerative diseases (NDDs). To comprehensively assess the effects of probiotics on clinical symptoms and systemic inflammation regulation in various NDDs, this systematic review conducted a detailed search of the Cochrane Library, Embase, PubMed, and Web of Science databases, ultimately including 22 eligible randomized controlled trials (RCTs), with 4 RCTs for Alzheimer’s Disease (AD), 10 RCTs for Parkinson’s Disease (PD), 2 RCTs for Multiple Sclerosis (MS), and 2 RCTs for Mild Cognitive Impairment (MCI), and intervention durations ranging from 4 to 16 weeks. The comprehensive analysis indicates that probiotics help improve clinical symptoms related to NDDs, including gastrointestinal function, cognitive function, quality of life, and mental health. Additionally, probiotics generally have a positive effect on reducing systemic inflammation and enhancing antioxidant capacity in patients. In conclusion, existing evidence supports the promising potential of probiotics in treating NDDs. However, further large-scale, high-quality studies are needed to explore specific differences in efficacy among various probiotic strains, dosages, and modes of administration. Moreover, considering that lifestyle and dietary habits may modulate the effects of probiotics, these external factors should also be included in research considerations to gain a more comprehensive understanding of the mechanisms and application strategies of probiotics in NDDs treatment.