Poor sleep quality and physical inactivity are known risk factors for depressive symptoms. Yet, whether these factors differently contribute to depressive symptoms and whether they interact with one another remains unclear. Here, we examined how sleep quality and physical activity influence depressive symptoms in 79,274 adults 50 years of age or older (52.4% women) from the Survey of Health, Aging and Retirement in Europe (SHARE) study. Sleep quality (poor vs. good), physical activity (inactive vs. active), and depressive symptoms (0 to 12 score) were repeatedly collected (7 waves of data collection) between 2004 and 2017. Results showed that sleep quality and physical activity were associated with depressive symptoms. Specifically, participants with poorer sleep quality reported more depressive symptoms than participants with better sleep quality (b = 1.85, 95% CI = 1.83-1.86, p < .001). Likewise, compared to physically active participants, physically inactive participants reported more depressive symptoms (b = 0.44, 95% CI = 0.42-0.45, p < .001). Moreover, sleep quality and physical activity showed an interactive association with depressive symptoms (b = 0.17, 95% CI = 0.13-0.20, p < .001). The negative association between poor sleep quality and higher depressive symptoms was stronger in physically inactive than active participants. These findings suggest that, in adults 50 years of age or older, both poor sleep quality and physical inactivity are related to an increase in depressive symptoms. Moreover, the detrimental association between poor sleep quality and depressive symptoms is amplified in physically inactive individuals.