The application of microorganisms as probiotics is limited due to lack of safety evaluation. Here, a novel multi-stress-tolerant yeast Meyerozyma guilliermondii GXDK6 with aroma-producing properties was identified from marine mangrove microorganisms. Its safety and probiotic properties were assessed in accordance with phenotype and whole-genome sequencing analysis. Results showed that the genes and phenotypic expression of related virulence, antibiotic resistance and retroelement were rarely found. Hyphal morphogenesis genes (SIT4, HOG1, SPA2, ERK1, ICL1, CST20, HSP104, TPS1, and RHO1) and phospholipase secretion gene (VPS4) were annotated. True hyphae and phospholipase were absent. Only one retroelement (Tad1-65_BG) was found. Major biogenic amines (BAs) encoding genes were absent, except for spermidine synthase (JA9_002594), spermine synthase (JA9_004690), and tyrosine decarboxylase (inx). The production of single BAs and total BAs was far below the food-defined thresholds. GXDK6 had no resistance to common antifungal drugs. Virulence enzymes, such as gelatinase, DNase, hemolytic, lecithinase, and thrombin were absent. Acute toxicity test with mice demonstrated that GXDK6 is safe. GXDK6 has a good reproduction ability in the simulation gastrointestinal tract. GXDK6 also has a strong antioxidant ability, β-glucosidase, and inulinase activity. To sum up, GXDK6 is considered as a safe probiotic for human consumption and food fermentation.