Ticks represent a primary group of public health and global economic relevance due to their high vector competence. During hematophagy, they secrete pharmacologically active molecules via salivary glands. Thus, this study aims to investigate the modulatory potential of the Salivary Gland Extract (SGE) from the tick Ornithodoros brasiliensis (Acari: Argasidae) (Aragão, 1923) on microbial growth, identifying molecules capable of promoting or inhibiting the cellular proliferation of specific microorganisms. Salivary glands were obtained from semi-engorged specimens (CEUA No. 4130270323) and subjected to maceration. The resulting extract was sterilized under a laminar flow hood using 0.22 µm filters (MilliPore). Protein concentration was quantified using a NanoDrop 2000 spectrophotometer (Thermo Scientific) at A280 nm. The SGE was evaluated against Staphylococcus aureus (ATCC 25923), Salmonella enterica (ATCC 14028), and Candida albicans (ATCC 10231). Antimicrobial activity assays were performed using broth dilution in Mueller- Hinton medium (for bacteria) or Sabouraud Dextrose broth (for yeasts), with absorbance measured at 595 nm in a Multiskan EX spectrophotometer (Thermo Fisher) after 20 hours of incubation at 37 °C. The SGE was subjected to reverse-phase high-performance liquid chromatography (RP-HPLC) using a Jupiter C18 column (20A Prominence, Shimadzu Co., Japan). Mass spectrometry analysis (Orbitrap Exploris 480), processed with PEAKS Studio 13 software, allowed the initial identification of proteins associated with the selected fractions. Protein sequences were retrieved and analyzed using BLASTp (Basic Local Alignment Search Tool for proteins) via the National Center for Biotechnology Information (NCBI) database. Microbiological assays demonstrated potent inhibitory activity against cellular growth for the three tested micr oorganisms: 100% inhibition of S. aureus in fractions F13 and I.3; 100% inhibition of S. enterica in fractions F2, F13, and I.3; and 50% and 70% inhibition of C. albicans in fractions F6 and I.3, respectively. Preliminary mass spectrometry analysis identified Arg r 1-like lipocalins (F2), acid-tailed salivary proteins (F13), hypothetical proteins (F6), and transporters involved in glycosylation processes (I.3). The presence of these proteins suggests a possible relationship between immunomodulatory mechanisms and the observed antimicrobial activity. Although detailed bioinformatic analysis is ongoing, the data obtained to date indicate that O. brasiliensis SGE constitutes a promising source of molecules with antimicrobial and biotechnological potential, justifying further investigations for the structural and functional characterization of the identified proteins Grants #2013/07467-1 and #2021/13939-0, São Paulo Research Foundation (FAPESP)