Background/Objectives: Dyslipidemia and hepatic lipid buildup are key features of cardiometabolic disorders caused by high-fat, high-cholesterol diets. Both curcumin and flaxseed oil have been shown to improve lipid metabolism through different mechanisms. This study examined the effects of combining curcumin with flaxseed oil on lipid metabolism in hamsters fed a high-fat, high-cholesterol diet and further investigated the underlying mechanisms using liver and serum lipidomic analyses. Methods: Thirty-two male Golden Syrian hamsters were randomly divided into four groups (n = 8 per group): control, high-fat/high-cholesterol diet (HFD), HFD with low-dose curcumin-flaxseed oil mixture, and HFD with high-dose curcumin-flaxseed oil mixture. After 8 weeks, serum lipid profiles, hepatic triglyceride (TG) and total cholesterol (TC), fecal TG and TC excretion, hepatic mRNA expression of SREBP-1, ACC, and FAS, and untargeted lipidomic profiles in serum and liver were analyzed. Results: Compared with the HFD group, curcumin-flaxseed oil supplementation significantly reduced serum TG, TC, and LDL-C levels, while HDL-C remained unchanged. Hepatic TG and TC accumulation also decreased significantly, accompanied by increased fecal TG and TC excretion, with a more pronounced effect in the high-dose group. Hepatic SREBP-1 and ACC mRNA expression increased in the low-dose group, whereas FAS expression remained unchanged. Lipidomic analysis showed notable remodeling of diacylglycerol species in both liver and serum. A similar trend was observed in serum TG profiles, particularly TG 54:1 and TG 52:2, suggesting that changes in circulating lipids may mirror the hepatic lipidomic response. Conclusions: Curcumin combined with flaxseed oil improved dyslipidemia and hepatic lipid accumulation in hamsters fed a high-fat, high-cholesterol diet, potentially through increased lipid excretion and modulation of hepatic and circulating lipid profiles.