Caffeine is an alkaloid present in a wide variety of plants. Currently the most consumed psychostimulant worldwide, its consumption is associated with several health benefits, including modulation of the innate and adaptive immune response, reduction of oxidative cellular stress, and decreased incidence of some cancers, including breast cancer. Breast cancer is the most common cause of cancer among women and the second leading cause of cancer death in women worldwide. The interaction between biomaterials and drugs has enabled a great advance in science for developing controlled drug delivery systems and has been used to treat numerous pathologies. This work aimed to evaluate the immunomodulatory effects of caffeine associated or not with polyethylene glycol adsorbed in microemulsion (MLP) on MCF-7 cells, phagocytic cells (MN), and coculture. For biological assays, ATCC (American Type Culture Collection, USA) cell lines of breast adenocarcinoma (MCF-7) and phagocytes (MN) obtained from voluntary donors were used. The cells (MN and MCF-7) and coculture were treated with caffeine and MLP and incubated for rheological characterization analyses: flow curve and viscosity, oxidative stress: superoxide anion assay (
), and activity of the enzyme superoxide dismutase (Cu-Zn-SOD). Caffeine and MLP increased viscosity and blood and MCF-7 cells and affected the immunomodulation of oxidative stress metabolism of MN and MCF-7 cells treated with caffeine and associated caffeine to the MLP. These data suggest that caffeine is associated or not with MLP-induced immunomodulatory effects on MN phagocytes and MCF-7 cells, demonstrating the antitumor activity via oxidative stress and can be a complementary alternative for treating breast cancer.