Advanced glycation end-products (AGEs) and their receptor cause diabetic liver disease by increasing oxidative stress and inflammation. We investigate the potential therapeutic benefits of Cirsium japonicum (CJ) in preventing the progression of diabetes, focusing on complications for both liver and kidney health associated with AGEs. Streptozotocin (STZ, 30 mg/kg) was injected into SD rats and CJ (50, 100 mg/kg) was orally administered for 4 weeks. CJ treatment led to a marked reduction in key diabetic markers (glucose, reaction oxygen species, and lactate dehydrogenase), compared with the rats treated only with STZ. Moreover, the hepatic tissues of STZ-treated rats exhibited heightened biomarkers associated with AGE induction and formation, and these were notably attenuated in the CJ-treated rats. This effectively alleviated oxidative stress, inflammation, and AGE accumulation in the liver. Similarly, in the context of diabetic nephropathy, CJ treatment resulted in significant improvements in the rats with STZ-induced diabetes. Biomarkers associated with AGE induction and formation were significantly reduced in CJ-treated rats, demonstrating the ability of CJ to combat renal oxidative stress, inflammation, and AGE-related complications in diabetic nephropathy. CJ thus shows potential as a promising natural remedy that might mitigate the detrimental effects of diabetes on both the liver and kidneys through its anti-oxidation, anti-inflammation, and anti-AGE activities. These findings suggest that CJ is a beneficial agent for preventing and treating diabetic complications.