Several studies suggest that different combinations of nutraceutical supplements may improve the lipid profile, representing a viable alternative to statins. However, their effects on individuals with myopathy need to be investigated. The aim of our study was to explore the mid- and long-term physiological effects of monacolin k (5 mg) and astaxanthin (0.1 mg) supplements in association with a low-energy/fat diet in a group of subjects with mild myopathy. Eighty subjects (44 women) took part in this observational study. Participants were assigned to the experimental group (EG, n = 40, 24 women) treated with a low-energy/fat diet (1200–1500 Kcal/day and 15–20% lipids) in combination with monacolin k (5 mg) and astaxanthin (0.1 mg) supplementation, and to the control group (CG, n = 40, 20 women) treated only with a low-energy/fat diet (1200–1500 Kcal/day and 15–20% lipids). BMI and biochemical parameters (blood glucose, total cholesterol, HDL, LDL, triglycerides, C-reactive protein (CRP) and creatine phosphokinase-CPK) were collected at baseline (T0), after 12 (T1) and 24 (T2) weeks. A mixed factorial ANOVA was performed to determine if there were significant main effects and/or interactions between time and treatment. Treatment (EG vs. CG) was entered as the between-subjects factor and time (T0 vs. T1 vs. T2) as the within-subject factor. We found a significant improvement in total cholesterol, HDL, LDL, PCR and CPK parameters in EG compared with CG. Our results highlight the efficacy and safety of combined use of monacolin k (5 mg) and astaxanthin (0.1 mg) in combination with a low-energy/fat diet in the treatment of dyslipidemia.