The Beta-glucan Effects on Lipid profile, glycemia and inTestinal health (BELT) Study investigated the effect of 3 g/day oat beta-glucans on plasma lipids, fasting glucose and self-perceived intestinal well-being. The Study was an 8-week, double-blind, placebo-controlled, cross-over randomized clinical trial, enrolling a sample of 83 Italian free-living subjects, adherent to Mediterranean diet, with a moderate hypercholesterolemia and a low cardiovascular risk profile. Beta-glucans reduced mean LDL-Cholesterol (LDL-C) levels from baseline by 12.2% (95%CI: −15.4 to −3.8) after 4 weeks of supplementation and by 15.1% (95%CI: −17.8 to −5.9) after 8 weeks of supplementation ( p < 0.01 for both comparison and versus placebo). Between baseline and 4 weeks Total Cholesterol (TC) levels showed an average reduction of 6.5% (95%CI: −10.9 to −1.9) in the beta-glucan sequence; while non-HDL-C plasma concentrations decreased by 11.8% (95%CI: −14.6 to −4.5). Moreover, after 8 weeks of beta-glucan supplementation TC was reduced by 8.9% (95%CI: −12.6 to −2.3) and non-HDL-C levels by 12.1% (95%CI: −15.6 to −5.3). Decreses in TC and non HDL-C were significant also versus placebo (respectively p < 0.05 and p < 0.01 to both follow-up visits). Fasting plasma glucose and self-perceived intestinal well-being were not affected by both beta-glucan and placebo supplementation.