Advanced glycation end products of BSA (AGE-BSA) contribute to the pathogenesis of diabetic vascular diseases. However, the roles and underlying mechanisms of AGE-BSA in diabetic vascular diseases remain largely unclear. Long non-coding RNAs (lncRNAs) are widely identified and known as gene regulators. However, the roles of lncRNAs in diabetic vascular disease are still vague. In this study, we sought to investigate the contributions of lncRNAs in human umbilical vein endothelial cells (HUVECs) treated with AGE-BSA. We first demonstrated that AGE-BSA reduced the cell viability and inhibited the cell proliferation of HUVECs. Then, we found that lncRNA MEG3 was up-regulated in HUVECs treated with AGE-BSA. Furthermore, inhibition of MEG3 restored the AGE-BSA-induced repression of cell viability and proliferation. In addition, our results revealed that MEG3 played its role via modulation of miR-93 expression in HUVECs treated with AGE-BSA. Furthermore, we illustrated that miR-93 played its role via regulation of p21 in HUVECs treated with AGE-BSA. Ultimately, our study displayed that AGE-BSA exerted its function via modulation of MEG3/miR-93/p21 pathway in HUVECs. Thus, for the first time, we identified the MEG3/miR-93/p21 axis in HUVECs treated with AGE-BSA, which might be a novel regulatory network in diabetic vascular cells, and possess the potential therapeutic value for diabetes mellitus.