Pioglitazone is a thiazolidinedione that can improve peripheral insulin sensitivity and reduce hepatic gluconeogenesis. However, in type 2 diabetes mellitus (T2DM) patients with advanced chronic kidney disease (CKD), pioglitazone has been overlooked. The study compared the all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE), and new-onset of end stage renal disease (ESRD) in type 2 DM patients with advanced chronic kidney disease between pioglitazone users and dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) users. DM patients older than 20 years old with advanced CKD between 2006 and 2016 were identified from the Taiwan’s National Health Insurance Research Database, and were further divided into two groups according to whether they received pioglitazone (pioglitazone group) or DPP4-inhibitors (Comparison group) in the following three months after the advanced CKD date. Propensity score stabilize weighting (PSSW) was used to balance the baseline characteristics between the two groups. The pioglitazone group (n = 2121) exhibited a lower rate (per person-years) of all-cause mortality (12.4% vs. 13.4%, HR: 0.87, 95% CI: 0.81–0.94), MACCEs-related mortality (4.6% vs. 4.7%, HR: 0.87, 95% CI: 0.77–0.98), infection-related mortality (7.5% vs. 8.1%, HR: 0.87, 95% CI: 0.77–0.98), and a marginally lower risk of MACCEs (10.9% vs. 12.4%, HR: 0.92, 95% CI: 0.85–1.00) compared with the comparison group (n =15325). The risk of new-onset ESRD requiring dialysis did not differ between the two groups. This study revealed that pioglitazone can safely reduce several adverse outcomes in DM patients with advanced CKD.