Soy sauce (Shoyu) is a traditional Japanese fermented seasoning and is available worldwide. We investigated the effects of Shoyu polysaccharides (SPS) prepared from soy sauce on hyperlipidemia in vitro and in vivo. First, SPS inhibited pancreatic lipase. Second, in experiments with animals, it was found that SPS reduced serum triacylglycerol (TG) elevation induced by high-fat diets. Third, in a 2-week placebo-controlled parallel group study, healthy men (TG <150 mg/dl) were treated with 600 mg of SPS (n=5) or placebo (n=5) every day. After 2 weeks, serum TG elevation was significantly (P<0.05) lower in the SPS-treated group than in the placebo-treated group after 6 h of a high-fat diet. Fourth, in a 4-week randomized, double-blind, placebo-controlled parallel group study, hyperlipidemic men (TG >150 mg/dl) were treated with 600 mg of SPS (n=15) or placebo (n=15) daily. After 4 weeks, serum TG levels in the SPS-treated group were significantly (P<0.05) lower than the baseline (0 week). In conclusion, SPS of soy sauce reduce lipid absorption, and soy sauce is a potentially promising seasoning for the treatment of hyperlipidemia through food.