Background Prostate cancer (PCa) is the most common cancer and the fifth leading cause of death in men worldwide. The treatment of PCa depends on the clinical stage of the disease, prostate-specific antigen (PSA) level, and histology. Lycopene is a bright red carotenoid found in tomatoes, which enhances apoptosis in prostate cells, but its effectiveness has not been studied in East African countries. This study aimed to determine the effectiveness of lycopene from tomato extracts in reducing PSA levels, disease progression, and apoptosis in the prostate glands of men with PCa in Tanzania. Methods This study will be a randomized phase III clinical trial of men diagnosed with PCa in Tanzania. In total, 400 men will be randomized in a 1:1 ratio to receive intervention (n=200) and control (n=200) and followed for 12 months. The intervention arm will receive tomato paste for daily use in addition to the standard treatment, whereas the control arm will only follow the standard of care. The primary endpoints will be a reduction in PSA levels, improved clinical status, and apoptosis of the prostate gland. Data analysis was performed based on the intention-to-treat principle. Descriptive statistics were used to compare average lycopene and PSA levels in the intervention group using T-test and Chi-squared tests. Generalized linear mixed models will be used to further assess the effect of lycopene on PCa progression, urinary symptoms, and PSA reduction. All statistical tests were two-sided at an alpha level of <0.05. Discussion The study used a food supplement as a drug/intervention with minimal or no adverse reactions. However, there is a fear that the control group may not adhere to the protocol after learning the benefits of tomato paste. The study findings will promote the consumption of tomato paste in males diagnosed with PCa to improve the clinical status and reduce disease progression. Trial registration The study has been registered at the Pan African Clinical Trial Registry with registration No PACTR202405488763956.