Metformin, a first-line drug used to treat patients with type 2 diabetes mellitus, has been studied for its metabolic, antiproliferative and pro-apoptotic effects in cancer patients. This study aimed to carry out a systematic review evaluating the effect of this drug in cancer patients, as well as to evaluate the clinical results obtained in cancer patients who used metformin independently or in association with other antineoplastic agents and to verify the possible mechanisms of action of metformin in tumor cells. Thus, a systematic review was carried out according to the protocol present in PRISMA, where the search string was defined using the PICOS approach. Articles in English and Portuguese, published from January 2002 to December 2022 in the following databases were selected: PubMed, Scielo, Lilacs, ScienceDirect, Springer and Wiley. 1,322 articles were identified through the search string and after excluding duplicate articles, it resulted in 1,311 articles for title and abstract reading. Next, 25 articles were included for complete reading and after the final analysis, 14 articles were included in the review. The selected articles indicate the potential effect of metformin in cancer patients, as well as better overall survival and disease-free survival. It was observed that metformin can exert its antiproliferative effect directly on tumor cells by activating the AMPK (AMP-activated protein kinase) enzyme which inhibits the mTOR (mammalian target of rapamycin) signaling pathway that is responsible for growth and cell proliferation. Furthermore, it was observed that metformin can act indirectly, which reduces circulating insulin levels and improves insulin sensitivity. Thus, it can be concluded that metformin has a significant antitumor effect in cancer patients, improving their overall survival, without triggering relevant adverse effects. The data demonstrate the potential antitumor effect of metformin both alone and in combination with other antineoplastic drugs.