Background: Studies regarding the impact of Parkinson's disease (PD) on quality of life (QOL) have reported conflicting results, and the underlying QOL domains require further study. In order to understand the association between PD and QOL, we conducted this meta-analysis to systematically compare QOL between PD patients and healthy controls. Method: The PubMed, PsycINFO, EMBASE, and Web of Science databases were systematically searched. Data were analyzed using the random-effects model. Results: Twenty studies covering 2707 PD patients and 150,661 healthy controls were included in the study. Compared with healthy controls, PD patients had significantly poorer QOL overall and in most domains with moderate to large effects sizes. Different QOL measures varied in their association with quality of life, with the Parkinson's Disease Questionnaire-39 (PDQ-39) having the largest effect size (standard mean difference, SMD = −1.384, 95% CI: −1.607, −1.162, Z = 12.189, P < 0.001), followed by the Europe Quality of Life Questionnaire-visual analogue scale (EQ-VAS) (SMD = −1.081, 95% CI: −1.578, −0.584, Z = −4.265, P < 0.001), Europe Quality of Life Questionnaire-5D (EQ-5D) (SMD = −0.889, 95% CI: −1.181, −0.596, Z = −5.962, P < 0.001), and the Short-form Health Survey (SF) scales (physical dimension: SMD = −0.826, 95% CI: −1.529, −0.123, Z = −2.303, P = 0.021; mental dimension: SMD = −0.376, 95% CI: −0.732, −0.019, Z = −2.064, P = 0.039). Conclusion: PD patients had lower QOL compared with healthy controls in most domains, especially in physical function and mental health. Considering the negative impact of poor QOL on daily life and functional outcomes, effective measures should be developed to improve QOL in this population.