Among chronically-ill older adults, the benefits of moderate-to-vigorous physical activity (MVPA) are established. Comorbid depressive symptoms and Major Depression are prevalent among the chronically-ill, but how different doses of MVPA may protect against depression remains understudied. Thus, using 10 years of data from The Irish Longitudinal Study on Ageing, we quantified longitudinal associations between MVPA doses and depressive symptoms and Major Depression among chronically-ill older adults living with type 2 diabetes (T2DM). Continuous MVPA (MET.min.week−1), three dose and five dose MVPA categories were examined. Depressive symptoms and Major Depression were measured using the center for Epidemiological Studies Depression and the Composite International Diagnostic Interview for Major Depressive Episode. Negative binomial regression and logistic models, adjusted for covariates, quantified associations across time. Among the 2,262 participants, those adhering to the WHO guidelines of 600-<1,200 MET.min.week−1 had 28% lower odds of Major Depression compared to those not achieving the guidelines (OR: 0.72; 95%CI: 0.53–0.98). For depressive symptoms, a higher MVPA dose was required with a 13% (IRR: 0.87; 95%CI: 0.82–0.93) lower rate of symptoms among those exceeding recommendations (1200-<2,400 MET.min.week−1). Interventions should focus on enhancing achievability of and compliance with these MVPA doses among the chronically-ill, including T2DM, to protect against depression.