This work investigated the use of water extract of green propolis (WEP) and its association with free or liposomal meglumine antimoniate (MA) for the treatment of murine visceral leishmaniasis. Mice infected with Leishmania infantum were treated with oral doses of WEP associated or not with a single dose of liposomal MA by intraperitoneal route. Parasite burden was assessed in the liver and spleen by limiting dilution assay, and alterations in the spleen cellular phenotype were evaluated by flow cytometry. Tissue damage was assessed by determination of biochemical markers of the liver, heart, and kidney function and histopathological analysis of the liver and spleen. Our data showed that treatment with WEP was able to reduce parasite load in the liver but not in the spleen. On the other hand, liposomal MA reduced parasite load in both organs. Unexpectedly, there was no synergism with the combination of WEP and liposomal MA in reducing the parasite load. The histopathological analysis showed that administration of WEP, liposomal MA, or their association was able to protect the liver and spleen from lesions caused by infection. No alteration in the profile of spleen cells by flow cytometry or in the liver, heart, and kidney functions by biochemical markers due to any of the treatments was observed. These results demonstrate that although WEP was able to significantly reduce the liver parasite load, its association with liposomal MA did not lead to significant improvement in reducing parasite load. On the other hand, treatment with WEP and/or liposomal MA protected the liver and spleen from lesions caused by the infection.