Background: Lycopene, a dietary carotenoid with antioxidant properties, protects against sun-induced skin damage, prostatic conditions such as chronic prostatitis, and cancer; however, its role in metabolic disorders, including metabolic syndrome and nonalcoholic fatty liver disease (MAFLD), remains unclear. This study aimed to systematically assess the association between lycopene levels (serum and dietary) and the risk of metabolic diseases. Methods: This study adhered to the PRISMA guidelines and was prospectively registered on the Open Science Framework (OSF). We searched PubMed, Scopus, Web of Science, and Medline via WoS. Pooled odds ratios (OR), hazard ratios (HR), and mean differences (MD) with 95% confidence intervals (CIs) were calculated using fixed or random-effects models based on heterogeneity. Results: Twenty-nine studies were included, of which twenty-five were eligible for the meta-analysis. Pooled analysis showed that the individuals with the lowest serum lycopene levels had a significantly higher risk of MAFLD (OR = 1.39, 95%CI: 1.02–1.89, p = 0.0388). No significant associations were found between HbA1c levels, diabetes history, and weight status. Although not statistically significant, a clear trend of patients with DM having lower lycopene levels than the control group was observed (MD = −0.09, 95% CI: −0.19 to 0.00, p = 0.054). Comparisons based on weight status showed no significant differences. Conclusions: While lower serum lycopene levels are significantly associated with increased MAFLD risk, their impact on glycemic control remains inconclusive, underscoring the need for targeted clinical research.