Therefore, this study was designed to determine metabolic reprogramming regarding L-arginine pathway enzymes in the colonic mucosa of CRC patients (ARG1, NOS2, DDAH1, DDAH2, PRMT1, and PRMT5) and to investigate the possible effect of selected oxicams on the pathway status in colorectal adenocarcinoma cell lines HCT 116, HT-29 and Caco-2, at the level of both metabolome (arginine, citrulline, ornithine, ADMA, SDMA, DMA, nitrates, and nitrites) and transcriptome (ARG2, NOS2, DDAH1, DDAH2, PRMT1, and PRMT5). Here, NOS2 is linked to colorectal adenocarcinoma.