Several randomized controlled trials (RCTs) have investigated the effect of lycopene supplementation on serum levels of prostate-specific antigen (PSA) in patients with prostate cancer. However, results have been inconclusive. We systematically searched PubMed, Embase, and Scopus up to January 2020 to find RCTs investigating the effect of lycopene supplementation on serum levels of PSA in patients with non-metastatic prostate cancer. Using a random-effects model, the reported risk estimates were pooled. A total of six trials were included in the final analysis. we found no significant effect of lycopene on circulating PSA (WMD: -0.60, 95% CI: -2.01, 0.81 µg/L). However, we observed a significant reducing effect when the analysis was confined to studies that included patients with higher baseline levels of PSA (≥6.5 µg/L) (WMD: -3.74 µg/L, 95% CI: -5.15, -2.32, P < 0.001). Subgroup analysis based on the duration of intervention did not result in any significant effect. Non-linear dose-response analysis did not show any significant effects of lycopene dosage (Pnon-linearity = 0.50) and duration of the intervention (Pnon-linearity = 0.63) on serum levels of PSA. Although lycopene supplementation did not produce any reduction in PSA levels overall, a significant reducing effect was observed in patients with higher levels of baseline PSA. Due to the heterogeneity of our results, further high-quality clinical trials with long-term duration are required to determine the efficacy of lycopene in patients with non-metastatic prostate cancer.