This work assessed the effects of a 28-day treatment with lycopene-rich extract (LRE) from red guava fruit (Psidium guajava L.) on the lipid profile and oxidative stress in an experimental model of dyslipidemia. Male hamsters (116.5 ± 2.16 g) were fed with the AIN 93G diet containing casein (20%), coconut fat (13.5%) and cholesterol (0.1%). The animals were divided into four groups: normolipidemic control (standard feed; NC, n = 7); hypercholesterolemic control (HC, n = 7); LRE 25 mg/kg/day (LRE-25, n = 7) and LRE 50 mg/kg/day (LRE-50, n = 9). After treatment, plasma concentrations of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL) cholesterol (LDL-c), high-density lipoprotein (HDL) cholesterol (HDL-c), malondialdehyde (MDA-p) and myeloperoxidase (MPO), as well as erythrocytic superoxide dismutase (SOD-e) and the atherogenic index, were determined. Malondialdehyde (MDA-h), catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD-h) levels were assessed. Feed intake (FI) and weight gain (WG) were also determined. The LRE-25 group presented significantly lower TG levels and atherogenic index than did the HC group (p < 0.05). Both LRE-25 and LRE-50 groups presented lower levels of MDA-p and MPO than did the HC group (p < 0.05). LRE demonstrated a promising effect against dyslipidemia and oxidative stress.