In previous studies, A-type procyanidin oligomers isolated from Cinnamomum tamala were proved to possess antidiabetic effect and protect pancreatic β-cells in vivo. The aim of this study was to unveil the mechanisms of protecting pancreatic β-cells from palmitic acid-induced apoptosis by cinnamtannin D-1 (CD1), one of the main A-type procyanidin oligomers in C. tamala. CD1 was discovered to dose-dependently reduce palmitic acid- or H2O2-induced apoptosis and oxidative stress in INS-1 cells, MIN6 cells, and primary cultured murine islets. Moreover, CD1 could reverse palmitic acid-induced dysfunction of glucose-stimulated insulin secretion in primary cultured islets. These results indicate that reduction of apoptosis and oxidative stress might account for the protection effect of CD1, which provided a better understanding of the mechanisms of the antidiabetic effects of procyanidin oligomers.