Shiitake (Lentinus edodes) is a culinary-medicinal mushroom that has low lipid content and is rich in protein, fiber, minerals, vitamins, antioxidant compounds, and β-glucans. We assessed the effects of L. edodes bars on cholesterolemia and oxidative stress levels in individuals with borderline high cholesterol through a randomized, double-blind, placebo-controlled study. Individuals with borderline high cholesterol, low-density lipoprotein, or triglycerides were recruited. Sixty-eight individuals were randomly allocated to group I (placebo; n = 32) or group II (intervention; n = 36). Blood samples were collected at 0, 33, and 66 days, and all individuals received an unidentified opaque envelope containing the bars. Biochemical (triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, and glucose) and oxidative stress biomarkers (reduced glutathione, catalase, and thiobarbituric acid reactive substances) in the blood were assessed. Participants in the intervention group showed a 10% reduction in triglycerides after 66 days of consuming the shiitake bars (P = 0.0352). In oxidative stress biomarkers, L. edodes increased the main endogenous antioxidant reduced glutathione and reduced lipid peroxidation. Exposure to L. edodes triggered dermatitis in 10% of individuals sensitive to the mushroom. In conclusion, L. edodes bars are a nutritious food and a functional health food alternative. This food improves redox status and can be considered as an adjuvant in the prevention of dyslipidemia.