The parasites of the genus Leishmania cause a range of leishmaniasis diseases, whose treatment is impaired due to intramacrophage parasites living in the mammalian host. Immunostimulation has been considered an important strategy to leishmaniasis treatment. The immunomodulatory effects of the polysaccharides arabinogalactan (ARAGAL), galactomannan (GMPOLY), and xyloglucan (XGJ), as well as their oxovanadium (IV/V) complexes (ARAGAL:VO, GMPOLY:VO, and XGJ:VO) were evaluated on peritoneal macrophages. At 25 μg/mL of GMPOLY:VO and of XGJ:VO, and 10 μg/mL of ARAGAL:VO, nitric oxide (NO) production by the macrophages was not altered compared with the control group. All polymers increased the production of interleukins 1 beta and 6 (IL-1β and IL-6), but the oxovanadium complexes were more potent activators of these mediators. ARAGAL:VO 10 μg/mL, GMPOLY:VO and XGJ:VO 25 μg/mL led to an increase of 562%, 1054%, and 523% for IL-1β, respectively. For IL-6 at the same concentration, the levels increased by 539% and 794% for ARAGAL:VO and GMPOLY:VO, respectively. Polysaccharides and their oxovanadium complexes exhibited important leishmanicidal effects on amastigotes of Leishmania (L.) amazonensis. The native and complexed polymers reduced the growth of promastigote-form Leishmania by ∼60%. This effect was reached at concentrations 12 times lower than that observed for Glucantime (300 μg/mL promoted an inhibition of ∼60%). The 50% inhibitory concentration (IC50) values for the complexes were determined. XGJ:VO showed the lowest IC50 value (6.2 μg/mL; 0.07 μg/mL of vanadium), which for ARAGAL:VO was 6.5 μg/mL (0.21 μg/mL of vanadium) and 7.3 μg/mL (0.06 μg/mL of vanadium) for GMPOLY:VO. The upregulation of IL-1β and IL-6 release and downregulation of NO production by macrophages and the important leishmanicidal effect are essential to stablish their potential use against this pathology.