This study investigated the chemical composition, immunomodulatory and antioxidant activities, and histopathological analysis of mice tissues treated with methanolic extract from R. marina poison. Marinobufagin, telecinobufagin and bufalin were identified in the chemical profile. The biochemical results demonstrated an effect between doses in the period of 7 days, an immunomodulatory effect was observed regarding the production capacity of interleukin (IL)-12p70 and tumor necrosis factor (TNF)-α at 7 and 30 days, respectively. The lower dose suggests better bioactivity to the treated animal than the higher dose. Histopathological analyses of the lung, heart, kidney and liver showed tissue damage in all organs, mainly in the lung, and were proportional to the dose and the treatment period. We observed that the treatment modulated cytokine production, and therefore this effect may be related to the tissue damage observed. This study demonstrates a positive effect in the antioxidant and immune system, indicating that the molecules found in the extract have biotechnological potential.