Actinobacteria are one of the largest bacterial phyla. These microbes produce bioactive compounds, such as antifungals, antibiotics, immunological modulators, and anti-tumor agents. Studies on actinobacteria isolated from the Brazilian Savannah biome (Cerrado) are scarce and mostly address metagenomics or the search for hydrolytic enzyme-producing microbes. (lobeira) is a tree widely employed in regional gastronomy and pharmacopeia in Central Brazil. In this work, 60 actinobacteria isolates were purified from the rhizosphere of . Eight spp. isolates were selected for in vitro antifungal activity against H99, the 89-610 fluconazole-tolerant strain, NIH198, , and . The ability of the aqueous extracts of the isolates to induce the in vitro secretion of tumor necrosis factor (TNF-α), nitric oxide (NO), interleukin-6 (IL-6), and IL-10 by murine macrophages was also evaluated. All extracts showed antifungal activity against at least two yeast species. spp. LAP11, LDB2, and LDB17 inhibited growth by 40-93%. Most extracts (except LAP2) also inhibited . None inhibited , but all inhibited (40-90%). sp. LAP8 extract increased nitric oxide production by approximately 347-fold in murine macrophages, while LDB11 extract suppressed LPS-induced TNF-α production by 70% and simultaneously increased IL-10 secretion, suggesting immunosuppressive potential. The results revealed that Cerrado actinobacteria-derived aqueous extracts are potential sources of antifungal and immunomodulatory biocompounds.