ABSTRACT: Navy beans contain bioactive phytochemicals with colon cancer prevention properties as demonstrated in carcinogen-induced animal models. Human studies support that dietary navy bean intake modulates metabolism by the gut microbiome. This study investigated the effect of navy bean ingestion on plasma and urine metabolite profiles of overweight and obese colorectal cancer survivors. Twenty participants completed a single-blinded, randomized-controlled dietary intervention with precooked navy beans (35 g bean powder/day) or control (0 g/day) for 4 weeks. Plasma and urine were collected at baseline, 2 weeks, and 4 weeks following consumption. Nontargeted metabolomics was applied to study meals and snacks, navy beans, plasma, and urine. Increased navy bean consumption was hypothesized to (i) delineate dietary biomarkers and (ii) promote metabolic shifts relevant for cancer protection in the plasma and urine metabolome. At 4 weeks, 16 plasma and 16 urine metabolites were significantly different in the navy bean intervention group compared with placebo control (P < 0.05). Increased plasma 2,3-dihydroxy-2-methylbutyrate (1.34-fold), S-methylcysteine (1.92-fold), and pipecolate (3.89-fold), and urine S-adenosylhomocysteine (2.09-fold) and cysteine (1.60-fold) represent metabolites with cancer-protective actions following navy bean consumption. Diet-derived metabolites were detected in plasma or urine and confirmed for presence in the navy bean intervention meals and snacks. These included 3-(4-hydroxyphenyl)propionate, betaine, pipecolate, S-methylcysteine, choline, eicosapentaenoate (20:5n3), benzoate, S-adenosylhomocysteine, N-delta-acetylornithine, cysteine, 3-(4-hydroxyphenyl)lactate, gentisate, hippurate, 4-hydroxyhippurate, and salicylate. The navy bean dietary intervention for 4 weeks showed changes to pathways of metabolic importance to colorectal cancer prevention and merit continued attention for dietary modulation in future high-risk cohort investigations. PREVENTION RELEVANCE: This clinical study suggests that increased consumption of navy beans would deliver bioactive metabolites to individuals at high risk for colorectal cancer recurrence and produce metabolic shifts in plasma and urine profiles.