One of the most commonly therapeutic implications of nano gold is treatment of small cancers especially during the early twentieth century, also melittin has been approved via many clinical trials as a valid therapeutic approach in several types of cancers. The present study was designed to investigate the possible therapeutic potential of nano gold and/or melittin. In vivo studies were performed on fifty colorectal carcinoma bearing mice which were allocated into five equal groups 10 rats of each, mice bearing colorectal carcinoma group, mice bearing colorectal carcinoma treated with melittin group, mice bearing colorectal carcinoma treated with nanogold group, mice bearing colorectal carcinoma treated with cisplatin group, mice bearing colorectal carcinoma treated with mixture of melittin and nanogold group. The gene expression analysis for P13K, PTEN, AKT, P53, mTOR, mir-21, histopathological and immunohistochemical analysis for cytokeratin were done. The result showed that PI3K, mTOR, and mir-21 levels upregulate in mice bearing colorectal carcinoma group while their levels downregulate in the other groups respectively. Otherwise TP53 and PTEN levels were downregulated in mice bearing colorectal carcinoma group while upregulated in the other groups respectively. So, these results showed that combining melittin with nano gold achieved a therapeutic potency like cisplatin with minimal hepatic and renal adverse effects followed by melittin and nano gold both In vivo and In vitro. It can be concluded that combination of nano gold with melittin can be used as a safe alternative for cisplatin in dealing with colorectal carcinoma.