Stimulating antitumor immunity is an attractive idea for suppressing tumors. CD4 + and CD8 + T cells as well as natural killer cells (NK) are the primary antitumor immune cells in the tumor microenvironment (TME). In contrast to these cells, regulatory T cells (Tregs), myeloid‐derived suppressor cells (MDSCs), cancer‐associated fibroblasts (CAFs), and tumor‐associated macrophages (TAMs) release several molecules to suppress antitumor immunity and stimulate cancer cell invasion and proliferation. Adjuvant treatment with certain nontoxic agents is interesting to boost antitumor immunity. Metformin, which is known as an antidiabetes drug, can modulate both antitumor and protumor immune cells within TME. It has the ability to induce the proliferation of CD8 + T lymphocytes and NK cells. On the other hand, metformin attenuates polarization toward TAMs, CAFs, and Tregs. Metformin also may stimulate the antitumor activity of immune system cells, while it interrupts the positive cross‐talk and interactions between immunosuppressive cells and cancer cells. The purpose of this review is to explain the basic mechanisms for the interactions and communications between immunosuppressive, anti‐tumoral, and cancer cells within TME. Next, we discuss the modulating effects of metformin on various cells and secretions in TME.